As filed with the Securities and Exchange Commission on March 16, 2001

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                   ----------

                                    FORM S-8
                             REGISTRATION STATEMENT
                        Under the Securities Act of 1933

                           HEMISPHERX BIOPHARMA, INC.
             (Exact name of registrant as specified in its charter)

        Delaware                       5417                     52-0845822
(State or other jurisdiction  (Primary Standard Industrial   (I.R.S. Employer
  of incorporation or          Classification Code Number)   Identification No.)
  organization)

                               1617 JFK Boulevard
                        Philadelphia, Pennsylvania 19103
                                 (215) 988-0080
    (Address and Telephone Number of Registrant's Principal Executive Office)
                                   (Zip Code)

              1990 AMENDED AND RESTATED EMPLOYEE STOCK OPTION PLAN
                        (460,798 shares of Common Stock)

             1992 AMENDED AND RESTATED EMPLOYEE STOCK PURCHASE PLAN
                         (92,160 shares of Common Stock)

             1993 AMENDED AND RESTATED EMPLOYEE STOCK PURCHASE PLAN
                        (138,240 shares of Common Stock)

                            (full title of the plans)

                William A. Carter, M.D., Chief Executive Officer
                           Hemispherx Biopharma, Inc.
                               1617 JFK Boulevard
                        Philadelphia, Pennsylvania 19103
                                 (215) 988-0080

  (Name, Address & Telephone number, including area code, of agent for service)

                                   ----------
                                   Copies to:

                               Gary W. Mair, Esq.
                       Silverman, Collura & Chernis, P.C.
                       381 Park Avenue South - Suite 1601
                            New York, New York 10016
                                 (212) 779-8600

                         CALCULATION OF REGISTRATION FEE
================================================================================
Title of Each Class   Amount to be     Proposed        Proposed     Amount of
of Securities to      Registered(4)    Offering        Aggregate    Registration
be Registered                          Price Per       Offering     Fee(2)
                                       Share(1)        Price
- --------------------------------------------------------------------------------
Shares of Common
Stock, $.001
par value                  691,198       $4.40        $3,041,271      $760

================================================================================
Total Registration
Fee                                                                    $760

================================================================================

(1)  Estimated  solely for the  purpose of  computing  the  registration  fee in
accordance with Rules 457(c) and 457(h) of the Securities Act by multiplying (1)
691,198,  the maximum  number of shares of common stock of the  Registrant to be
issued  pursuant  to the  exercise  of  options  granted  under  the  Hemispherx
Biopharma, Inc. 1990, 1992 and 1993 Employee Stock Purchase Plans, by (2) $4.40,
the  average of the bid and asked  prices of the  shares of common  stock of the
Registrant reported on the American Stock Exchange on March 12, 2001.




(2) The registration fee has been calculated  pursuant to Rules 457(c)and 457(h)
of the  Securities  Act by  multiplying  (1)  $3,041,271,  the proposed  maximum
aggregate offering price by (2) .00025.

(3) In addition,  pursuant to Rule 416(c) under the Securities Act of 1933, this
registration  statement also covers an  indeterminate  amount of interests to be
offered or sold pursuant to the Hemispherx  Biopharma,  Inc. 1991, 1992 and 1993
Employee Stock Purchase Plans  described in this  registration  statement.  Plus
such  additional  number of shares  as may be  required  in the event of a stock
dividend,  stock split,  recapitalization  or other  similar event in accordance
with Rule 416(a) of the Securities Act of 1933.

(4)  Represents  the  maximum  number of shares of Common  Stock  issuable  upon
exercise of options  granted or to be granted  under the  Hemispherx  Biopharma,
Inc. 1991, 1992 and 1993 Stock Purchase Plans.




                                     PART I

                                Plan Information.

Item 1.

      This Form S-8 relates to 691,198  shares of common stock,  par value $.001
per share, of Hemispherx Biopharma,  Inc., which may be issued upon the exercise
of options  granted under the Hemispherx  Biopharma,  Inc.  1990,  1992 and 1993
Employee Stock Purchase Plans.

      The  documents  containing  information  required  in  the  Section  10(a)
prospectus  specified in Part 1 (plan  information  and registrant  information)
will be sent  or  given  to  employees  as  specified  by Rule  428(b)(1).  Such
documents need not be filed with the Securities and Exchange  Commission  either
as  part  of  this  registration  statement  or as  prospectuses  or  prospectus
supplements pursuant to Rule 424. These documents and the documents incorporated
by reference in this registration statement pursuant to Item 3 of Part 2 of this
form taken  together  constitute a  prospectus  that meets the  requirements  of
Section 10(a) of the Securities Act of 1933, as amended.

       Registrant Information And Stock Purchase Plan Annual Information.

Item 2.

      We file annual,  quarterly and special reports, proxy statements and other
information with the Securities and Exchange  Commission.  You may read and copy
any document we file at the  Commission's  public reference rooms in Washington,
D.C., New York, NY and Chicago, IL. Please call the Commission at 1-800-SEC-0330
for further  information on the public reference  rooms. Our Commission  filings
are  also   available  to  the  public  from  the   Commission's   web  site  at
http://www.sec.gov.  The  Commission  allows us to  "incorporate  by  reference"
information into this registration  statement,  which means that we can disclose
important  information  to  you  by  referring  you to  another  document  filed
separately  with the Commission.  The  information  incorporated by reference is
considered to be part of this registration statement, and later information that
we  file  with  the  Commission  will  automatically  update  this  registration
statement.

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

                    Incorporation Of Documents By Reference.

Item 3.

      We incorporate by reference the following  documents  listed below and any
future filings made with the Commission under Sections 13(a), 13(c), 14 or 15(d)
of the  Securities  Exchange  Act of  1934,  prior  to  the  termination  of the
offering:




      1. A  description  of  our  common  stock  contained  in our  registration
statement on Form S-1, File No. 333-08941, and any amendment or report filed for
the purpose of updating this  description  filed  subsequent to the date of this
prospectus and prior to the termination of this offering;

      2. our annual report on Form 10-K/A for our fiscal year ended December 31,
1999 (File No. 0-27072 and filing date of March 29, 2000);

      3. our quarterly  report on Form 10-Q for the quarterly period ended March
31, 2000 (File No. 0-27072 and filing date of May 5, 2000);

      4. our current  report on Form 8-K filed with the SEC on May 11, 2000, for
the event of May 3, 2000, (File No. 0-27072);

      5. our current  report on Form 8-K filed with the SEC on May 22, 2000, for
the event of May 3, 2000, (File No. 0-27072);

      6. our current  report on Form 8-K filed with the SEC on June 6, 2000, for
the event of May 3, 2000, (File No. 0-27072);

      7. our current report on Form 8-K filed with the SEC on July 12, 2000, for
the event of May 3, 2000, (File No. 0-27072);

      8. our current report on Form 8-K filed with the SEC on July 13, 2000, for
the event of May 3, 2000, (File No. 0-27072);

      9. our proxy  statement on schedule 14A for the 2000 annual  meeting (File
No. 0-27072 and filing date of July 13, 2000); and

      10.  quarterly report on Form 10-Q for the quarterly period ended June 30,
2000 (File No. 0-27072) and filing date of August 14, 2000.

      11. quarterly report on Form 10-Q for the quarterly period ended September
30, 2000, (File No. 0-27072) and filing date of November 14, 2000.

      All documents filed by the Registrant  pursuant to Sections 13(a),  13(c),
14 and  15(d) of the  Securities  Exchange  Act of 1934  after  the date of this
registration statement and prior to the filing of a post-effective  amendment to
this  registration  statement,  which  indicates  that  all  securities  offered
hereunder have been sold, or which  de-registers  all securities  then remaining
unsold under this registration statement,  shall be deemed to be incorporated by
reference in this  registration  statement and to be a part hereof from the date
of filing of such documents.


                                      -2-


      You should  rely only on the  information  incorporated  by  reference  or
provided  in  this  registration  statement  or  any  supplement.  We  have  not
authorized  anyone else to provide you with  different  information.  We and the
selling stockholders will not make offers of these shares in any state where the
offer is not  permitted.  You  should not assume  that the  information  in this
registration  statement or any  supplement is accurate as of any date other than
the date on the front of those documents.

      Any  statement  contained  in a document or  incorporated  or deemed to be
incorporated  by  reference  shall be deemed to be  modified or  superseded  for
purposes of this registration statement to the extent that a statement contained
herein or in any  subsequently  filed  document which also is or is deemed to be
incorporated by reference  herein  modifies or supersedes  such  statement.  Any
statement so modified or superseded  shall not be deemed,  except as so modified
or  superseded,  to  constitute  a part or  this  registrations  statement.  All
information in this  registration  statement is qualified in its entirety by the
information and financial statements (including the notes thereto).

      You may  request  a copy of these  filings,  at no  cost,  by  writing  or
telephoning us at the following address:  Hemispherx  Biopharma,  Inc., 1617 JFK
Boulevard, Philadelphia, Pennsylvania 19103, telephone number (215) 988-0080.

                            Description of Securities

Item 4.

Not Applicable.

                     Interests of named experts and counsel.

Item 5.

      The  legality  of the shares  offered  hereby has been passed upon for the
Company by Silverman,  Collura & Chernis, P.C., 381 Park Avenue South, New York,
New York 10016.

                   Indemnification of directors and officers.

Item 6.

      Section  145(a) of the  General  Corporation  Law of the State of Delaware
provides  that a Delaware  corporation  may indemnify any person who was or is a
party  or is  threatened  to be  made a  party  to any  threatened,  pending  or
completed action, suit or proceeding, whether civil, criminal, administrative or
investigative  (other than an action by or in the right of the  corporation)  by
reason of the fact that he is or was a director,  officer,  employee or agent of
the  corporation  or is or was  serving at the request of the  corporation  as a
director,  officer,  employee  or agent of another  corporation  or  enterprise,
against expenses,  judgments,  fines and amounts paid in settlement actually


                                      -3-


and  reasonably  incurred  by  him in  connection  with  such  action,  suit  or
proceeding if he acted in good faith and in a manner he  reasonably  believed to
be in or not opposed to the best interests of the corporation, and, with respect
to any criminal  action or  proceeding,  had no cause to believe his conduct was
unlawful.

      Section  145(b)  provides  that a Delaware  corporation  may indemnify any
person  who  was or is a  party  or is  threatened  to be  made a  party  to any
threatened,  pending  or  completed  action  or suit by or in the  right  of the
corporation  to procure a judgment  in its favor by reason of the fact that such
person acted in any of the capacities set forth above, against expenses actually
and reasonably  incurred by him in connection  with the defense or settlement of
such  action  or  suit if he  acted  under  similar  standards,  except  that no
indemnification may be made in respect of any claim, issue or matter as to which
such person shall have been adjudged to be liable to the corporation  unless and
only to the extent that the court in which such action or suit was brought shall
determine that despite the adjudication of liability,  such person is fairly and
reasonably  entitled to be  indemnified  for such expenses which the court shall
deem proper.

      Section 145 further  provides that (i) to the extent a director or officer
of a  corporation  has been  successful  in the defense of any  action,  suit or
proceeding  referred  to in  subsections  (a) and (b) or in the  defense  of any
claim,  issue,  or matter  therein,  he shall be  indemnified  against  expenses
actually  and  reasonably  incurred  by  him  in  connection   therewith,   (ii)
indemnification provided for by Section 145 shall not be deemed exclusive of any
other  rights to which the  indemnified  party  may be  entitled,  and (iii) the
corporation  may  purchase  and  maintain  insurance  on behalf of a director or
officer  of the  corporation  against  any  liability  asserted  against  him or
incurred  by him in any such  capacity  or  arising  out of his  status  as such
whether or not the  corporation  would have the power to  indemnify  him against
such liabilities under Section 145.

      Section  102(b)(7)  of  the  General   Corporation  Law  provides  that  a
corporation in its original certificate of incorporation or an amendment thereto
validly  approved by stockholders  may eliminate or limit personal  liability of
the  members  of its  board of  directors  or  governing  body for  breach  of a
director's fiduciary duty. However, no such provision may eliminate or limit the
liability of a director  for  breaching  his duty of loyalty,  failing to act in
good faith,  engaging in  intentional  misconduct or knowingly  violating a law,
paying a  dividend  or  approving  a stock  repurchase  which  was  illegal,  or
obtaining an improper personal  benefit.  A provision of this type has no effect
on the availability of equitable remedies,  such as an injunction or rescission,
for breach of fiduciary duty. Our charter contains such a provision.

      Our charter  further  provides  that we shall  indemnify  our officers and
directors and, to the extent authorized by the board of directors, employees and
agents of ours to the fullest extent permitted by and in the manner  permissible
under the laws of the State of Delaware.

      Our directors'  and officers'  liability  insurance  policy is designed to
reimburse us for payments made by us pursuant to the foregoing indemnification.


                                      -4-


      This  summary is subject to the  General  Corporation  Law of the State of
Delaware, our charter and the by-laws and the agreements referred to above.

                       Exemption from Registration Claimed

Item 7.

Not applicable.

                                    Exhibits

Item 8.

Unless  otherwise  noted the  following  exhibits have been filed with this Form
S-8.

4.1 1990 Employee Stock Option Plan

4.2 1992 Employee Stock Purchase Plan

4.3 1993 Employee Stock Purchase Plan

5.1 Opinion of Silverman, Collura & Chernis, P.C.

23.1  Consent  of  Silverman,  Collura  &  Chernis,  P.C.  to be  named  in  the
Registration  Statement.  Reference is made to Exhibit 5.1 to this  Registration
Statement which includes such consent.

23.2 Consent of KPMG, LLP.

                                  Undertakings

Item 9.

(a) The undersigned registrant hereby undertakes;

      (1) To file,  during any period in which offers or sales are being made, a
post-effective amendment to the Registration Statement;

      (i)  To  include  any  prospectus  required  by  Section  10(a)(3)  of the
Securities Act;


                                      -5-


      (ii) To reflect in the  prospectus  any facts or events  arising after the
effective date of this Registration Statement (or the most recent post-effective
amendment  thereof)  which,  individually  or  in  the  aggregate,  represent  a
fundamental change in the information set forth in the Registration Statement;

      (iii) To include  any  material  information  with  respect to the plan of
distribution  not  previously  disclosed  in the  Registration  Statement or any
material change of such information in the Registration Statement;

      Provided however that paragraphs  (a)(1)(i) and (a)(1)(ii) shall not apply
to information contained in periodic reports filed by the registrant pursuant to
Section  13 or  Section  15(d) of the  Exchange  Act that  are  incorporated  by
reference in this Registration Statement.

      (2)  That,  for  the  purpose  of  determining  any  liability  under  the
Securities Act, each such  post-effective  amendment shall be deemed to be a new
registration  statement  relating to the  securities  offered  therein,  and the
offering of such  securities at that time shall be deemed to be the initial bona
fide offering thereof.

      (3) To remove from registration by means of a post effective amendment any
of the securities being registered which remain unsold at the termination of the
offering.

      (b) The undersigned  registrant  hereby  undertakes  that, for purposes of
determining  any  liability  under  the  Securities  Act,  each  filing  of  the
registrant's  annual  report  pursuant to section  13(a) or section 15(d) of the
Exchange Act that is  incorporated by reference in this  Registration  Statement
shall be deemed to be a new  registration  statement  relating to the securities
offered herein, and the offering of such securities at that time shall be deemed
to be the initial bona fide offering thereof.

      (c)  Insofar  as  indemnification   for  liabilities   arising  under  the
Securities Act may be permitted to directors,  officers and controlling  persons
of the  registrant  pursuant  to the  foregoing  provisions  or  otherwise,  the
registrant  has  been  advised  that  in the  opinion  of the  Commission,  such
indemnification  is against public policy as expressed in the Securities Act and
is,  therefore,  unenforceable.  In the event  that a claim for  indemnification
against such  liabilities  (other than the payment by the registrant of expenses
incurred or paid by a director,  officer or controlling person of the registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director,  officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been  settled by  controlling  precedent,  submit to a court of  appropriate
jurisdiction the question whether such  indemnification is against public policy
as  expressed  in  the  Securities  Act  and  will  be  governed  by  the  final
adjudication of such issue.


                                      -6-


                                   SIGNATURES

      Pursuant to the requirements of the Securities Act of 1933, the registrant
certifies  that it has  reasonable  grounds to believe  that it meets all of the
requirements  for  filing  on Form S-8 and has  duly  caused  this  registration
statement  to be  signed  on its  behalf  by  the  undersigned,  thereunto  duly
authorized, in the city of Philadelphia state of Pennsylvania,  on this 13th day
of March, 2001.

                                            HEMISPHERX BIOPHARMA, INC.

                                       By:  /s/ William A. Carter
                                            ---------------------
                                            William A. Carter, President and CEO

      Pursuant  to  the  requirements  of  the  Securities  Act  of  1933,  this
registration  statement  has  been  signed  by  the  following  persons  in  the
capacities and on the dates indicated.


                                      -7-


                                POWER OF ATTORNEY

      KNOW ALL  PERSONS BY THESE  PRESENTS,  that each  person  whose  signature
appears  below  constitutes  and appoints  William A. Carter his true and lawful
attorney-in-fact  and agent, with full power of substitution and resubstitution,
for him and in his name, place and stead, in any and all capacities, to sign any
or all amendments  (including  post-effective  amendments)  to the  registration
statement on Form S-8, and to file the same, with all exhibits thereto,  and all
documents in connection therewith,  with the Securities and Exchange Commission,
granting unto said  attorney-in-fact  and agent,  full power and authority to do
and perform each and every act and thing  requisite  and necessary to be done in
and about the  premises,  as fully to all  intents  and  purposes as he might or
could  do  in  person,   hereby   ratifying   and   confirming   all  that  said
attorney-in-fact and agent, or his substitute or substitutes, may lawfully do or
cause to be done by virtue hereof.

Signature                              Title                           Date
- ---------                              -----                           ----

/s/ William A. Carter         Principal Executive Officer         March 9, 2001
- -----------------------       and Chairman of the Board
William A. Carter, M.D.       and as Power of Attorney
                              for Members of the Board

/s/ Robert E. Peterson        Principal Financial Officer and     March 9, 2001
- -----------------------       Principal Accounting Officer
Robert E. Peterson

/s/ Richard C. Piani          Director                            March_12, 2001
- -----------------------
Richard C. Piani

/s/ Ransom W. Etheridge       Director                            March 9, 2001
- -----------------------
Ransom W. Etheridge

/s/ William Mitchell          Director                            March 12, 2001
- -----------------------
William Mitchell


                                      -8-


                                Index to Exhibits

Unless  otherwise  noted the  following  exhibits have been filed with this Form
S-8.

4.1 1990 Amended and Restated Employee Stock Option Plan

4.2 1992 Amended and Restated Employee Stock Purchase Plan

4.3 1993 Amended and Restated Employee Stock Purchase Plan

5.1 Opinion of Silverman, Collura & Chernis, P.C.

23.1  Consent  of  Silverman,  Collura  &  Chernis,  P.C.  to be  named  in  the
Registration  Statement.  Reference is made to Exhibit 5.1 to this  Registration
Statement which includes such consent.

23.2 Consent of KPMG, LLP.