MacroChem Corporation
                              40 Washington Street
                                   Suite 220
                           Wellesley Hills, MA 02481


                                      BERNARD R. PATRIACCA
                                      Vice President and Chief Financial Officer





February 23, 2007


Mr. Jim B. Rosenberg
Senior Assistant Chief Accountant
Division of Corporation Finance
Mail Stop 6010
United States Securities and Exchange Commission
Washington, DC 20549

      RE:  MACROCHEM CORPORATION
           FORM 10-K FOR THE YEAR ENDED DECEMBER 31, 2005
           FILE NO. 0-13634

Dear Mr. Rosenberg:

Set forth below is a response of MacroChem Corporation ("MACROCHEM" or the
"COMPANY") to the Commission's Oral Comments conveyed during a telephone
conference with SEC Senior Staff Accountant Mark Brunhofer on February 12, 2007
that pertain to MacroChem's Annual Report on Form 10-K for the year ended
December 31, 2005 (File No. 0-13634) (the "FORM 10-K") filed on March 28, 2006.

The responses below are keyed to the comment numbers referenced in the telephone
conference with the Commission.

FORM 10-K FOR THE YEAR ENDED DECEMBER 31, 2005



FINANCIAL STATEMENTS

NOTE 4:  STOCKHOLDERS' EQUITY

AUTHORIZED CAPITAL STOCK, PAGE 55
STOCK SALES, PAGE 55

1.   COMMENT: PLEASE PROVIDE US A DRAFT DISCLOSURE AS TO WHY YOU CLASSIFY YOUR
     SERIES C PREFERRED STOCK IN THE MEZZANINE CONSISTENT WITH YOUR RESPONSE TO
     OUR PREVIOUS COMMENT 2A.

Mr. Jim B. Rosenberg                  -2-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          RESPONSE:

          SERIES C CONVERTIBLE PREFERRED STOCK

          On December 23, 2005, pursuant to the terms of a Preferred Stock and
          Warrant Purchase Agreement (the "Purchase Agreement"), the Company
          completed the first closing of a private placement (the "Series C
          Financing") in which institutional investors (the "Purchasers")
          acquired 250 shares of Series C Cumulative Convertible Preferred Stock
          (the "Series C Preferred Stock") and six-year Warrants to purchase
          2,380,951 shares of common stock at an exercise price of $1.26 per
          share, for an aggregate purchase price of $2.5 million (the "First
          Closing"). The net proceeds from the First Closing were $2,125,943. In
          the second closing of the Series C Financing, on February 13, 2006,
          the Company issued to institutional investors (the "Purchasers") 575.5
          shares of Series C Preferred Stock and six-year warrants (the
          "Warrants") to purchase 5,480,961 shares of the Company's common stock
          at an exercise price of $1.26 per share, for an aggregate purchase
          price of approximately $5.75 million (the "Second Closing"). The net
          proceeds from the Second Closing were $5,186,908. The terms of the
          Series C Preferred Stock and Warrants issued in the First Closing and
          the Second Closing were identical.

          RELEVANT MATERIAL TERMS

          The terms and provisions of the Series C Preferred Stock are set forth
          in the Certificate of Designations, Rights and Preferences of Series C
          Cumulative Convertible Preferred Stock (the "Certificate of
          Designations"). Certain material terms of the Series C Preferred Stock
          relevant to this response are summarized below:

          OBLIGATIONS TO REGISTER SHARES

          When issued, the securities offered and sold to the Purchasers in the
          Series C Financing were not registered under the Securities Act of
          1933, as amended (the "Securities Act") and were sold in reliance upon
          the exemption from securities registration afforded by Regulation D
          under the Securities Act. All of the Purchasers represented to
          MacroChem that they were "accredited investors", as defined in Rule
          501 of Regulation D. In connection with the Series C Financing,
          MacroChem entered into an Investor Rights Agreement with the
          Purchasers, pursuant to which MacroChem was required to file a
          registration statement with the Securities and Exchange Commission
          covering the resale of the common stock issuable upon conversion of
          the Series C Preferred Stock, issuable as payment of dividends on the
          Series C Preferred Stock and issuable upon exercise of the Warrants

Mr. Jim B. Rosenberg                  -3-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          and the warrants issued to the placement agent, no later than March
          27, 2006, and to use its best efforts to cause the registration
          statement to become effective within a specified time period. The
          Investor Rights Agreement further provides that if a registration
          statement is not filed or declared effective within specified time
          period, the Company would be required to pay each holder an amount in
          cash, as liquidated damages, equal to 2.0% per month of the aggregate
          purchase price paid by such holder in the private placement for the
          common stock and warrants then held.

          DIVIDENDS: The Series C Preferred Stock accrues dividends at the rate
          of 10% of the stated price annually, payable quarterly in cash or
          common stock. The first dividend payment date was March 31, 2006.

          LIQUIDATION: Upon liquidation, dissolution or winding up, the holders
          of Series C Preferred Stock are entitled, before any distributions are
          made to the holders of the common stock, or any other class or series
          of capital stock of the Company ranking junior to the Series C
          Preferred Stock as to such distributions, to be paid an amount equal
          to $10,000 per share and any unpaid dividends thereon, subject to
          adjustment.

          VOTING: The Certificate of Designations contains a provision that
          restricts a holder of Series C Preferred Stock from (i) converting
          Series C Preferred Stock into common stock to the extent that such
          conversion would result in the holder owning more than 4.95% of the
          issued and outstanding common stock of the Company or (ii) voting
          together with the common stock on an as-if-converted to common stock
          basis in respect of more than 4.95% of the issued and outstanding
          common stock of the Company. The Warrants issued pursuant to the
          purchase agreement contain a similar restriction (collectively, the
          "Beneficial Ownership Cap"). A holder of Series C Preferred Stock or a
          Warrant may elect, subject to certain conditions, to be exempt from
          the Beneficial Ownership Cap. Subject to the Beneficial Ownership Cap
          restrictions, as of the date of the second closing of the private
          placement financing in February 2006 (the "Second Closing"), the
          Series C Preferred Stock acquired by the purchasers was convertible
          into 4,057,885 shares of common stock and the holders of the Series C
          Preferred Stock vote on an as-converted basis with the holders of our
          common stock, and therefore held approximately 80.28% of the voting
          power of our outstanding securities. Assuming both the conversion of
          the Series C Preferred Stock and the exercise of all of the Warrants
          acquired by the purchasers, in each case subject to the Beneficial
          Ownership Cap restrictions, the purchasers would have held
          approximately 89.06% of the outstanding common stock of the Company as
          of the date of the Second Closing.


Mr. Jim B. Rosenberg                  -4-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          REDEMPTION: If the Company fails or refuses to convert any shares of
          Series C Preferred Stock in accordance with the terms of the Series C
          Preferred Stock, the holders of the Series C Preferred Stock are
          entitled to elect to require the Company to redeem their Series C
          Preferred Stock. In the event of a redemption, the redemption price
          per share of Series C Preferred Stock is an amount in cash equal to
          the greater of (1) all accrued but unpaid dividends as of the date the
          holder makes the demand for redemption with respect to each share to
          be redeemed plus the $10,000 liquidation preference per share or (2)
          the total number of shares of common stock into which such Series C
          Preferred Stock is convertible multiplied by the then-current market
          price of the common stock.

          Given that the redemption provision described above does not embody an
          unconditional obligation requiring the Company to redeem the
          instrument at a specified or determinable date or upon an event
          certain to occur, the Series C Preferred Stock is not a mandatorily
          redeemable financial instrument. Therefore, the Company determined
          that the guidance in FAS 150, ACCOUNTING FOR CERTAIN FINANCIAL
          INSTRUMENTS WITH CHARACTERISTICS OF BOTH LIABILITIES AND EQUITY, which
          requires liability classification for mandatorily redeemable financial
          instruments, does not apply.

          Rule 5-02.28 of Regulation S-X requires securities with redemption
          features that are not solely within the control of the issuer to be
          classified outside of permanent equity. The holders of the Series C
          Preferred Stock control a majority of the voting power of the
          Company's common stock and, as a result of this control, could
          directly or indirectly influence the triggering of the redemption
          provision by, for example, refusing to approve an increase in the
          authorized but unissued shares of common stock of the Company if, in
          the future, such increase were necessary to effect the conversion of
          the Series C Preferred Stock. Accordingly, the redemption provision is
          not solely within the Company's control, and thus the Series C
          Preferred Stock is not permanent equity.

          Because the Series C Preferred Stock did not qualify for treatment as
          a liability or as permanent equity as described above, the Company
          recorded the portion of the proceeds attributable to the Series C
          Preferred Stock as mezzanine equity pursuant to EITF Topic D-98,
          Classification and Measurement of Redeemable Securities. Because the
          Company has a substantial amount of authorized but unissued common
          stock (in excess of 95 million shares), the occurrence of a redemption
          event is not considered probable, and thus the carrying value of the
          Series C Preferred Stock was not accreted to its redemption value.

          CONVERSION: Each convertible preferred share is convertible into
          shares of common stock. The number of shares of common stock into

Mr. Jim B. Rosenberg                  -5-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          which each share of Series C Preferred Stock is convertible is
          determined by dividing the liquidation value per share plus all
          accrued but unpaid dividends thereon by $1.05. The conversion price
          for the Series C Preferred Stock and the Warrant exercise price were
          each subject to reset adjustment such that if the average price of the
          common stock over the twenty trading days immediately preceding May 8,
          2006 (the "Average Price") was lower than the conversion and/or
          exercise price, then such conversion and/or exercise price would have
          been adjusted to equal the Average Price.

          The Company evaluated whether the embedded conversion feature in the
          Series C Preferred Stock required bifurcation and determined, in
          accordance with paragraph 12 of SFAS 133, that the economic
          characteristics and risks of the embedded conversion feature in the
          Series C Preferred Stock were clearly and closely related to the
          underlying common stock because, through the voting and conversion
          rights, the holders of Series C Preferred Stock essentially control
          the Company. As a result, the Company concluded that bifurcation was
          not required under SFAS 133.

          Pursuant to the guidance in paragraph 5 of EITF 00-27, APPLICATION OF
          ISSUE NO. 98-5 TO CERTAIN CONVERTIBLE INSTRUMENTS, we allocated the
          proceeds from the Series C financing between the Series C Preferred
          Stock and the warrants based upon their estimated fair values as of
          the closing date resulting in $330,243 being allocated to the Series C
          Preferred Stock and $1,620,778 being allocated to the warrants. We
          then calculated the intrinsic value of the beneficial conversion
          feature embedded in the Series C Preferred Stock. As the amount of the
          beneficial conversion feature exceeded the value allocated to the
          Series C Preferred Stock, the amount of the beneficial conversion
          feature recorded was limited to the proceeds allocated to the Series C
          Preferred Stock. The beneficial conversion value of $330,243 was
          recognized as an additional discount on the Series C Preferred Stock
          which amount was immediately accreted and treated as a deemed dividend
          to the holder of the shares of Series C Preferred Stock as all of the
          Series C Preferred Stock was eligible for conversion upon issuance.


          WARRANTS: In addition to the issuance of shares of Series C Preferred
          Stock, the Company issued warrants to purchase an aggregate of up to
          2,380,951 shares of common stock at a per share exercise price of
          $1.26 per share. The warrants have a term of exercise expiring in 6
          years. The warrants contain a "cashless exercise" feature that allows
          the holders, under certain circumstances, to exercise the warrants
          without making a cash payment to the Company. In addition, upon the
          occurrence of a change of control, a warrant holder, at its option,

Mr. Jim B. Rosenberg                  -6-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          can require the Company to repurchase the warrant for an aggregate
          purchase price, payable in cash, calculated according to a specified
          formula (the "Put Feature").

          The Company allocated the proceeds between the stock and the warrants
          based upon their estimated fair values as of the closing date,
          resulting in $1,620,778 being allocated to the warrants. The Company
          determined the fair value of the warrants using the Black-Scholes
          option pricing model with the following assumptions: weighted average
          risk free rate of 4.18%; volatility of 100% and a dividend yield of
          0%. The Company determined that the warrants meet the definition of a
          derivative instrument as defined in SFAS 133, Accounting for
          Derivative Instruments and Hedging Activities. The fair value of the
          warrants are recorded as liabilities pursuant to the guidance in
          paragraphs 12 and 27 of EITF 00-19, ACCOUNTING FOR DERIVATIVE
          FINANCIAL INSTRUMENTS INDEXED TO, AND POTENTIALLY SETTLED IN, A
          COMPANY'S OWN STOCK, because the Put Feature is a form of net cash
          settlement in that it allows a holder of the warrant to require the
          Company to repurchase the warrant for cash in the event of a change in
          control.

          OFFERING COSTS: The placement agent in the Series C Financing received
          a warrant to purchase approximately 238,905 shares of common stock at
          a purchase price of $1.05 per share for a period of 6 years. The
          Company determined the fair value of the warrants using the
          Black-Scholes option pricing model with the following assumptions:
          weighted average risk free rate of 4.18%; volatility of 100% and a
          dividend yield of 0%. The fair value of the warrants of $174,922 was
          treated as an offset to the proceeds of the Series C Financing and
          credited to additional paid in capital.


2.   COMMENT: WE ACKNOWLEDGE YOUR RESPONSE TO OUR PREVIOUS COMMENT 2B. PLEASE
     PROVIDE US DRAFT DISCLOSURE THAT CLEARLY EXPLAINS WHY YOU DO NOT BELIEVE
     REDEMPTION IS PROBABLE AND THEREFORE WHY YOU DO NOT ACCRETE YOUR SERIES C
     PREFERRED STOCK TO ITS REDEMPTION VALUE AS REQUIRED BY PARAGRAPH 15 OF
     EITF-D98.

          RESPONSE: Please see the response to Comment 1 above under the heading
          "Redemption", which contains consolidated draft disclosure.


3.   COMMENT: WE ACKNOWLEDGE YOUR RESPONSE TO OUR PREVIOUS COMMENT 2D AND IT IS
     UNCLEAR WHY YOU BELIEVE THE EMBEDDED CONVERSION FEATURE OF YOUR SERIES C
     PREFERRED STOCK IS "CLEARLY CONSIDERED TO POSSESS EQUITY CHARACTERISTICS"
     AND THEREFORE NOT A DERIVATIVE UNDER SFAS 133 AS A RESULT OF PARAGRAPH
     12(A). CONSISTENT WITH THE GUIDANCE IN PARAGRAPH 61(L) OF SFAS 133, IT
     APPEARS THAT YOUR CUMULATIVE FIXED NET DIVIDEND OF 10% AND YOUR POTENTIAL
     REDEMPTION REQUIREMENT ARE MORE AKIN TO DEBT. AS A RESULT, PLEASE PROVIDE

Mr. Jim B. Rosenberg                  -7-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

     AN ANALYSIS OF EACH OF THE CRITERIA OF PARAGRAPHS 12-32 OF EITF-0019 OR
     EXPLAIN TO US IN DETAIL HOW THE PROVISIONS OF YOUR PREFERRED STOCK ARE MORE
     AKIN TO EQUITY. IN YOUR ASSESSMENT, PLEASE NOTE THAT THE PROVISIONS OF
     PARAGRAPH 19 OF EITF-0019 MUST BE ASSESSED ON THE ISSUANCE DATE WITHOUT
     REGARD TO THE FACT THAT NO ADJUSTMENT TO THE CONVERSION RATE WAS ACTUALLY
     MADE ON MAY 8, 2006.

          RESPONSE: The Company supplementally advises the Staff that, while we
          recognize that the cumulative fixed dividend and the potential
          redemption requirement are characteristics of debt, when all of the
          economic characteristics and risks are considered as a whole, we
          concluded that the Series C Preferred Stock is more akin to equity
          than to debt. Pursuant to paragraph 60 of SFAS 133, "if the host
          contract encompasses a residual interest in an entity, then its
          economic characteristics and risks should be considered that of an
          equity instrument. . . ." Further in paragraph 60, the example points
          out that an instrument that does not "involve any existing or
          potential residual rights" would not be an equity instrument. The
          Series C Preferred Stock clearly gives the stockholders both existing
          and ongoing rights of ownership (i.e., a residual interest), as the
          holders of Series C Preferred Stock are entitled to vote on an
          as-converted basis with the holders of our common stock. The dividend,
          while fixed, is payable quarterly in cash or common stock at the
          Company's election. To date, the Company's Board of Directors has
          declared each quarterly dividend to be paid in shares of common stock.
          The redemption rights of the Series C preferred stock are perpetual
          and do not have a stated maturity or redemption date, unlike debt
          instruments. The right of the holders of the Series C Preferred stock
          to receive payments, including the Liquidation Preference, is not
          secured by any collateral.


4.   COMMENT: WE ACKNOWLEDGE YOUR RESPONSE TO OUR PREVIOUS COMMENT 2E AND WILL
     EVALUATE YOUR RESPONSE AGAIN AFTER YOU ADDRESS COMMENT 3 ABOVE. HOWEVER, IN
     ANY REGARD, PLEASE EXPLAIN TO US YOUR ACCOUNTING ENTRIES FOR THE ISSUANCE
     OF YOUR PREFERRED STOCK AND WARRANTS. IN THIS REGARD, IT IS UNCLEAR HOW YOU
     ALLOCATED THE $2,125,943 GROSS PROCEEDS IDENTIFIED IN YOUR STATEMENT OF
     CASH FLOWS AS YOUR RESPONSE ONLY INDICATED THAT A TOTAL OF $1,951,021 WAS
     ALLOCATED TO WARRANTS AND PREFERRED STOCK. IN ADDITION, WE WOULD EXPECT TO
     SEE A CREDIT TO ADDITIONAL PAID-IN CAPITAL FOR YOUR BENEFICIAL CONVERSION
     FEATURE THAT YOU RECOVERED UNDER EITF-0027.

          RESPONSE:

          Pursuant to the guidance in paragraph 5 of EITF 00-27, APPLICATION OF
          ISSUE NO. 98-5 TO CERTAIN CONVERTIBLE INSTRUMENTS, we allocated the
          proceeds from the Series C Financing on December 23, 2005, between the
          Series C Preferred Stock and the warrants based upon the their
          estimated fair values as of the closing date, resulting in $330,243

Mr. Jim B. Rosenberg                  -8-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

          being allocated to Series C Preferred Stock and $1,620,778 being
          allocated to the warrants. The remaining $174,922 of gross proceeds
          represented the value of the warrants issued to the placement agent in
          partial payment of its fees in connection with the transaction and
          were credited to Additional Paid in Capital. We then calculated the
          intrinsic value of the beneficial conversion feature embedded in the
          Series C Preferred Stock. As the amount of the beneficial conversion
          feature exceeded the value allocated to the Series C Preferred Stock,
          the amount of the beneficial conversion feature recorded was limited
          to the proceeds allocated to the Series C Preferred Stock. The
          beneficial conversion of $330,243 was recognized as an additional
          discount on the Series C Preferred Stock which amount was immediately
          accreted and treated as a deemed dividend to the holder of the shares
          of Series C Preferred Stock as all of the Series C Preferred Stock was
          eligible for conversion upon issuance.

          The following entries were recorded to properly reflect the Series C
          Preferred Stock transaction.


          Dr.
          Cash                                       2,500,000
          ------------------------------------------------------------------
                     Cr. Series C Preferred Stock                    330,243
          ------------------------------------------------------------------
                     Cr. Warrants liability                        1,620,778
          ------------------------------------------------------------------
                     Cr. APIC (Warrant to private                    174,922
                     placement agent)
          ------------------------------------------------------------------
                     Cr. Cash/A/P (issuance costs)                   374,057
          ------------------------------------------------------------------
          To record the sale of Preferred Stock and warrants at relative fair
          value
          ------------------------------------------------------------------


          ------------------------------------------------------------------
          Dr. Series C Preferred Stock               330,243
          ------------------------------------------------------------------
                     Cr. Additional Paid in Capital                  330,243
          ------------------------------------------------------------------
          To record Beneficial Conversion Feature of the Preferred Stock
          ------------------------------------------------------------------


          ------------------------------------------------------------------
          Dr. Additional Paid in Capital             330,243
          ------------------------------------------------------------------
                     Cr. Series C Preferred Stock                    330,243
          ------------------------------------------------------------------
          To recognize BCF and accrete preferred stock as deemed dividend.
          ------------------------------------------------------------------


Mr. Jim B. Rosenberg                  -9-                      February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance


WARRANTS, PAGE 55

5.   COMMENT: CONSISTENT WITH THE REASONS IDENTIFIED IN YOUR RESPONSE TO OUR
     PREVIOUS COMMENT 3, PLEASE PROVIDE US A REVISED DRAFT DISCLOSURE INDICATING
     WHY YOU ACCOUNT FOR YOUR WARRANTS AS LIABILITIES.

          RESPONSE: Please see the response to Comment 1 above under the heading
          "Warrants", which contains consolidated draft disclosure.


6.   COMMENT: WE ACKNOWLEDGE YOUR RESPONSE TO OUR PREVIOUS COMMENT 4. PLEASE
     EXPLAIN TO US WHY YOU BELIEVE THE VALUE OF THE PLACEMENT AGENT WARRANTS IS
     PROPERLY RECORDED AS A CREDIT TO ADDITIONAL PAID IN CAPITAL. IN THIS
     REGARD, PLEASE CLARIFY WHETHER THESE WARRANTS HAVE THE SAME PUT FEATURE
     IDENTIFIED IN YOUR RESPONSE TO OUR PREVIOUS COMMENT 3.

          RESPONSE: As of December 31, 2005, the value of the placement agent
          warrant for the Series C Financing, as described under the heading
          "Offering costs" in the response to Comment 1, was $174,922 which was
          credited to Additional Paid in Capital as it was considered a fee
          associated with the Series C Financing. Upon further review, we
          determined that the rights and obligations of the warrant issued to
          the placement agent are in substance the same as those of the warrants
          issued as part of the Series C Financing, including the Put Feature.
          As such, the warrants issued to the placement agent should have been
          credited to the warrant liability to be consistent with the treatment
          of the warrants issued as part of the financing. We will correct the
          error in our Annual Report on Form 10-K for the year ended December
          31, 2006 and will properly adjust the information presented in the
          footnote disclosures. The 2006 quarterly results included in the 2007
          Form 10-Q's will also be adjusted to reflect the correction of the
          error.


In connection with these responses to your comments, the Company acknowledges
that:

     o    the Company is responsible for the adequacy and accuracy of the
          disclosure in the filing;

     o    staff comments or changes to disclosure in response to staff comments
          do not foreclose the Commission from taking any action with respect to
          the filing; and

     o    the Company may not assert staff comments as a defense in any
          proceeding initiated by the Commission or any person under the federal
          securities laws of the United States.

Mr. Jim B. Rosenberg                  -10-                     February 23, 2007
Senior Assistant Chief Accountant-Division of Corporation Finance

Please direct any comments or questions on MacroChem's responses to me at (781)
489-7310. Thank you.

Sincerely,

/s/ Bernard R. Patriacca

Bernard R. Patriacca

cc:  Robert J. DeLuccia
     Glenn E. Deegan
     Dwight W. Quayle
     Justin A. McCormack