EXECUTION COPY

                   SECOND AMENDMENT TO STOCKHOLDERS' AGREEMENT

         THIS  SECOND  AMENDMENT  is  dated as of June 29,  2001  (this  "SECOND
AMENDMENT")  to the  Stockholders'  Agreement  dated as of March  30,  1999,  as
amended (the "STOCKHOLDERS Agreement"), by and among OraSure Technologies,  Inc.
(as  successor  to  STC  Technologies,   Inc.),  a  Delaware   corporation  (the
"COMPANY"),  and  the  Investors  identified  therein.   Capitalized  terms  not
otherwise  defined  herein shall have the  respective  meanings set forth in the
Stockholders' Agreement.

         WHEREAS,  the  Stockholders'  Agreement  provides  the  Investors  with
certain  rights and the parties now desire to supplement  and amend the terms of
the Stockholders' Agreement pursuant to the terms of this Second Amendment.

         NOW,  THEREFORE,  in  consideration  of the  premises  and  the  mutual
covenants  contained  herein  and other  good and  valuable  consideration,  the
receipt and  sufficiency of which are hereby  acknowledged,  and intending to be
legally bound, the Company and the Investors hereby agree as follows:

         1. Limitations on Registration Rights; Holdback.

              (a) The Company may delay the filing,  delay the  effectiveness or
suspend the  effectiveness  of a registration  statement of the Company covering
Restricted   Shares  as  contemplated  by  Sections  3.4,  3.5  or  3.6  of  the
Stockholders'  Agreement or  otherwise  prepared by the Company  (including  any
shelf  registration  statement  on Form  S-3) (a  "REGISTRATION  STATEMENT")  or
require the  Investors  to suspend  sales or other  dispositions  of  Restricted
Shares under an effective Registration  Statement, in each case for such time as
may be required by the  Company,  if (i) in the  Board's  judgment,  the sale of
Restricted Shares thereunder would interfere with or be detrimental to a planned
offering by the Company of any of the Company's securities,  (ii) in the Board's
judgment, the sale of Restricted Shares thereunder would have a material adverse
effect on the business, prospects,  operations,  results of operations,  assets,
liabilities,  or condition  (financial or  otherwise) of the Company;  (iii) the
Company is engaged in discussions  concerning any possible merger,  acquisition,
financing, business combination, restructuring or sale of all or any substantial
portion of the Company or its assets,  or any  similar  transaction  or (iv) the
Company would be required to disclose in such  Registration  Statement  material
information  that it would not  otherwise be required to disclose in its filings
with  the  Commission  pursuant  to the  Exchange  Act and  that it has not then
disclosed  in such  filings  with  the  Commission  (each an  "ALLOWED  DELAY").
Notwithstanding the foregoing, the Company shall not be entitled to exercise its
right  to  defer  filing  or  effectiveness  of or to  suspend  sales  or  other
dispositions  under a  Registration  Statement  pursuant to an Allowed Delay for
more than ninety (90)  consecutive  days. In the event of an Allowed Delay,  the
Company shall promptly (x) notify the Investors in writing (a "DELAY Notice") of
the  existence  (but not the  substance) of the Allowed Delay and (y) advise the
Investors  in  writing  to cease  all  sales or other  dispositions  under  such
Registration  Statement  until the expiration of the period  provided for in the
Delay  Notice.  To the extent  required  by the  Stockholders'  Agreement,  upon
expiration  of the Allowed  Delay,  the Company shall again be required to file,
cause the  effectiveness  of, or permit the resumption of sales and dispositions
under the Registration Statement.

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              (b)  If  the  Company  shall  at  any  time  register  any  of its
securities  under the Securities Act, for offer or sale to the public,  then the
Investors  shall  not  make  any  short  sale,  assignment,   transfer,  pledge,
hypothecation,  gift or other disposition (including the grant of any option for
sale)  of any  Restricted  Shares  (other  than  for the  public  sale of  those
Restricted  Shares included in and sold pursuant to such  registration)  without
the prior written consent of the Company for such period as may be designated by
the  Company  and,  if the  registration  shall  be,  in whole  or in  part,  an
underwritten  offering,  the managing underwriter;  provided that no such period
shall begin more than ten (10) days prior to the effectiveness of a Registration
Statement pursuant to which such public offer or sale will be made and shall not
last more than ninety (90) days after the  effective  date of such  Registration
Statement.

              (c) The Company shall use its commercially  reasonable  efforts to
keep any Registration Statement covering Restricted Shares effective, including,
but not limited to, preparing and filing with the Commission such amendments and
supplements to such Registration Statement and the prospectus used in connection
therewith  as may be  necessary to keep such  Registration  Statement  effective
until the earlier of (i) the sale of all Restricted  Shares  covered  thereby or
(ii) two years  following the  effective  date of such  Registration  Statement.
Notwithstanding  the  foregoing,  the  Company's  obligations  pursuant  to this
Section  1(c) and  Section 3 of the  Stockholders  Agreement  are subject to the
terms of Section 1(a) hereof.

         2. Obligations of the Investors. In connection with any registration of
the Restricted Shares, each of the Investors shall:

              (a) furnish to the Company such information  regarding itself, the
Restricted  Shares  held by it and the  intended  method of  disposition  of the
Restricted Shares held by it as shall be reasonably requested by the Company and
shall execute such documents in connection with such registration as the Company
may reasonably request;

              (b)  cooperate  with the Company as  reasonably  requested  by the
Company  in  connection  with  the  preparation  and  filing  of a  Registration
Statement or any amendment or supplement thereto;

              (c) upon  receipt of any notice from the Company of the  happening
of any  event  of the kind  described  in  Section  3.7(e)  of the  Stockholders
Agreement,  immediately discontinue disposition of Restricted Shares pursuant to
a Registration  Statement  covering such Restricted  Shares until the Investor's
receipt of the copies of the supplemented or amended prospectus  contemplated by
such Section  3.7(e) and, if so directed by the Company,  deliver to the Company
(at the  expense of the  Company)  or  destroy  (and  deliver  to the  Company a
certificate  of  destruction)  all copies in the Investor's  possession,  of the
prospectus covering such Restricted Shares current at the time of receipt of the
notice of the happening of an event as described in such Section 3.7(e);

              (d) upon receipt of any Delay Notice,  immediately discontinue the
sale or  disposition  of Restricted  Shares until the  expiration of the Allowed
Delay or any extension thereof pursuant to a subsequent Delay Notice; and

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              (e) comply with all applicable  laws and regulations in connection
with any sale, transfer or other disposition of Restricted Shares.

         3. Indemnification. Each prospective seller, and any underwriter acting
on its behalf,  of Restricted  Shares  registered  pursuant to any  Registration
Statement  prepared by the Company,  whether or not pursuant to Section 3 of the
Stockholders'  Agreement,  will  indemnify and hold harmless (in the same manner
and to the same  extent as set  forth in  Section  3.9(a)  of the  Stockholders'
Agreement)  the  Company,  each  director of the  Company,  each  officer of the
Company who signs such  Registration  Statement  and any person who controls the
Company  within the meaning of the  Securities  Act,  with respect to any untrue
statement  or  omission  from  such  Registration  Statement,   any  preliminary
prospectus or final prospectus contained therein, or any amendment or supplement
thereto,  if such untrue  statement or omission was made in reliance upon and in
conformity  with  written  information  furnished  to  the  Company  through  an
instrument duly executed by such seller or such underwriter specifically for use
in the preparation of such Registration Statement, preliminary prospectus, final
prospectus  or  amendment or  supplement;  provided,  however,  that the maximum
amount of liability in respect of such indemnification  shall be limited, in the
case of each prospective seller, to an amount equal to the net proceeds actually
received by such prospective  seller from the sale of Restricted Shares effected
pursuant to such Registration Statement.

         4.  Acknowledgment  of Obligations.  Each prospective  seller,  and any
underwriter  acting on its behalf, of Restricted  Shares registered  pursuant to
any Registration  Statement prepared by the Company,  whether or not pursuant to
Section  3 of  the  Stockholders'  Agreement,  shall  be  bound  by  all  of the
applicable  terms and  provisions set forth in the  Stockholders'  Agreement and
this Second Amendment.

         5. Termination of Certain Provisions.  Sections 2.1, 2.2,  2.4(a)(xiv),
2.4(b),  2.4(c),  2.7(e)(i),  2.9, and 2.12 of the  Stockholders'  Agreement are
hereby  terminated  in their  entirety  and neither the Company nor any Investor
shall have any further rights or obligations under such Sections.

         6. Miscellaneous.

              (a) Successors and Assigns. Except as otherwise expressly provided
in the Stockholders'  Agreement or this Second Amendment,  the provisions of the
Stockholders'  Agreement and this Second  Amendment  shall bind and inure to the
benefit of the Company and each of the Investors and the  respective  successors
and  assigns  of  the  Company  and  each  of  the  Investors.  Subject  to  the
requirements of Section 3 of the Stockholders'  Agreement, the Restricted Shares
held by the  Investors  and all of the rights and  obligations  set forth in the
Stockholders  Agreement  and this Second  Amendment may be freely  assigned,  in
whole or in part,  by each  Investor  to any  member of such  Investor's  Group;
provided,  however,  upon the acceptance any Restricted Shares by any transferee
of the Investor, such transferee shall automatically be bound by the obligations
imposed under the Stockholders'  Agreement and this Second Amendment to the same
extent  as if such  transferee  were an  Investor.  Upon  any such  transfer  of
Restricted  Shares by an Investor,  such Investor  shall, as a condition to such
transfer,  deliver to the Company a written notice of such proposed  transfer by
which such the transferee is and the securities of the Company owned or acquired
by such transferee are  identified.  A

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transferee to whom rights are transferred  pursuant to this Section 6(a) will be
thereafter  deemed to be an Investor  for the purpose of the  execution  of such
transferred rights and may not again transfer such rights to any other person or
entity,  other than as provided in this Section 6(a). Neither this Agreement nor
any of the rights or duties of the Company set forth herein shall be assigned by
the Company,  in whole or in part,  without  having  first  received the written
consent  of the  Investors  holding  a  majority  of  the  voting  power  of the
outstanding  Series A  Preferred  Shares held by all  Investors,  with each such
holder entitled to the number of votes for each such share of Series A Preferred
Stock as equals  the  number of shares  of Common  Stock  (including  fractional
shares)  into  which  each  such  share  of  Series  A  Preferred  Stock is then
convertible, rounded up to the nearest one-tenth of a share.

              (b) Except as otherwise  provided  herein,  the  provisions of the
Stockholders' Agreement, including, but not limited to, Section 3 thereof, shall
remain  in  full  force  and  effect.  To  the  extent  that  the  terms  of the
Stockholders'  Agreement  conflict with the terms of this Second Amendment,  the
terms of this Second Amendment shall control.

              (c)  The   Stockholders'   Agreement  and  this  Second  Amendment
constitute  the entire  agreement  among the parties  hereto with respect to the
subject  matter  hereof.  There are no  restrictions,  promises,  warranties  or
undertakings, other than those set forth or referred to herein and therein.

              (d)  Failure of any party to  exercise  any right or remedy  under
this Second Amendment or otherwise, or delay by a party in exercising such right
or remedy, shall not operate as a waiver thereof.

              (e) This  Second  Amendment  shall be  enforced,  governed  by and
construed in accordance  with the laws of the State of Delaware,  without giving
effect to conflict of laws  principles.  In the event that any provision of this
Second  Amendment is invalid or  unenforceable  under any applicable  statute or
rule of law, then such provision shall be deemed  inoperative to the extent that
it may  conflict  therewith  and shall be deemed  modified to conform  with such
statute or rule of law.

              (f)  This  Second  Amendment  may  be  executed  in  two  or  more
counterparts,  each of which shall be deemed an original  but all of which shall
constitute one and the same agreement. This Second Amendment, once executed by a
party, may be delivered to the other party hereto by facsimile transmission of a
copy of this Second  Amendment  bearing the signature of the party so delivering
this Second  Amendment.  This Second Amendment shall be effective upon execution
by the  holders  of  not  less  than  fifty  percent  (50%)  of the  outstanding
Restricted Shares pursuant to Section 11 of the Stockholders' Agreement.

              (g)  Each  party  shall  do and  perform,  or cause to be done and
performed,  all such further acts and things,  and shall execute and deliver all
such other  agreements,  certificates,  instruments and documents,  as the other
party may reasonably request in order to carry out the intent and accomplish the
purposes of this  Second  Amendment  and the  consummation  of the  transactions
contemplated hereby.

                            [SIGNATURE PAGE FOLLOWS]

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         IN WITNESS  WHEREOF,  the  Company and the  Investors  have caused this
Second Amendment to be duly executed as of the date first above written.

                               ORASURE TECHNOLOGIES, INC.

                                      By:  /s/ Robert D. Thompson
                                      Name:  Robert D. Thompson
                                      Title:  Chief Executive Officer


                               HEALTHCARE VENTURES V, L.P.

                                By:  HealthCare Partners V, its General Partner

                                      By:  /s/ Jeffrey Steinberg
                                      Name:  Jeffrey Steinberg
                                      Title:  Administrative Partner


                               HUDSON TRUST

                                      By:---------------------------------------
                                      Name:-------------------------------------
                                      Title:------------------------------------


                               PENNSYLVANIA EARLY STAGE PARTNERS, L.P.

                                By:  Pennsylvania Early Stage Partners GP,
                                L.L.C., its General Partner

                                      By:  /s/ Michael Bolton
                                      Name:  Michael Bolton
                                      Title:  Managing Director


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