METRA BIOSYSTEMS, INC.

                                       and

                        THE FIRST NATIONAL BANK OF BOSTON

                                  Rights Agent










                               AMENDMENT NO. 1 TO 

                        PREFERRED SHARES RIGHTS AGREEMENT


                          Dated as of January 17, 1997





                                  AMENDMENT NO. 1
                                         TO
                          PREFERRED SHARES RIGHTS AGREEMENT



     This Amendment No. 1 to Preferred Shares Rights Agreement, dated January 
17, 1997, amends that certain Preferred Shares Rights Agreement (the "Rights 
Agreement"), dated as of August 21, 1996 between Metra Biosystems, Inc., a 
California corporation (the "Company"), and The First National Bank of Boston 
(the "Rights Agent").

     On January 17, 1997, the Company's Board of Directors authorized an 
amendment of the Rights Agreement to increase certain threshold percentages 
required for a Person (as defined in the Rights Agreement) to become 
Acquiring Person (as defined in the Rights Agreement).

     NOW, THEREFORE, in consideration of the promises and the mutual 
agreements herein set forth, the parties hereby agree as follows:

     1.   Section 1(a) of the Rights Agreement is hereby amended and restated 
to read in full as follows:

          (a)  "Acquiring Person" shall mean any Person who or which, 
together with all Affiliates and Associates of such Person, shall be the 
Beneficial Owner of 20% or more of the Common Shares then outstanding, but 
shall not include the Company, any Subsidiary of the Company or any employee 
benefit plan of the Company or of any Subsidiary of the Company, or any 
entity holding Common Shares for or pursuant to the terms of any such plan. 
Notwithstanding the foregoing, no Person shall be deemed to be an Acquiring 
Person either (i) as the result of an acquisition of Common Shares by the 
Company which, by reducing the number of shares outstanding, increases the 
proportionate number of shares beneficially owned by such Person to 20% or 
more of the Common Shares of the Company then outstanding; PROVIDED, HOWEVER, 
that if a Person shall become the Beneficial Owner of 20% or more of the 
Common Shares of the Company then outstanding by reason of share purchases by 
the Company and shall, after such share purchases by the Company, become the 
Beneficial Owner of any additional Common Shares of the Company, then such 
Person shall be deemed to be an Acquiring Person; or (ii) if the Board of 
Directors of the Company determines in good faith that a Person who would 
otherwise be an "Acquiring Person" as defined pursuant to the foregoing 
provisions of this paragraph (a) has become such inadvertently, and such 
Person divests as promptly as practicable of a sufficient number of Common 
Shares so that such Person would no longer be an "Acquiring Person," as 
defined pursuant to the foregoing provisions of this paragraph (a).

     2.   Section 3(c) of the Rights Agreement is hereby amended and restated 
to read in full as follows:

          (c)  Unless the Board of Directors, by resolution adopted at or 
before the time of the issuance (including pursuant to the exercise of rights 
under the Company's benefit plans) of any Common Shares, specifies to the 
contrary, Rights shall be issued in respect of all Common 

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Shares that are issued after the Record Date but prior to the earlier of the 
Distribution Date or the Expiration Date or, in certain circumstances 
provided in Section 22 hereof, after the Distribution Date. Certificates 
representing such Common Shares shall also be deemed to be certificates for 
Rights, and shall bear the following legend:

     This certificate also evidences and entitles the holder hereof to certain 
     rights as set forth in a Rights Agreement between Metra Biosystems, Inc. 
     and The First National Bank of Boston as the Rights Agent, dated as of 
     August 21, 1996, as amended (the "Rights Agreement"), the terms of which 
     are hereby incorporated herein by reference and a copy of which is on file 
     at the principal executive offices of Metra Biosystems, Inc. Under certain 
     circumstances, as set forth in the Rights Agreement, such Rights will be 
     evidenced by separate certificates and will no longer be evidenced by this 
     certificate. Metra Biosystems, Inc. will mail to the holder of this 
     certificate a copy of the Rights Agreement without charge after receipt of 
     a written request therefor. Under certain circumstances set forth in the 
     Rights Agreement, Rights issued to, or held by, any Person who is, was or 
     becomes an Acquiring Person or any Affiliate or Associate thereof (as such 
     terms are defined in the Rights Agreement), whether currently held by or on
     behalf of such Person or by any subsequent holder, may become null and 
     void.

With respect to such certificates containing the foregoing legend, until the 
earlier of (i) the Distribution Date or (ii) the Expiration Date, the Rights 
associated with the Common Shares represented by such certificates shall be 
evidenced by such certificates alone, and the surrender for transfer of any 
such certificate shall also constitute the transfer of the Rights associated 
with the Common Shares represented thereby. In the event that the Company 
purchases or acquires any Common Shares after the Record Date but prior to 
the Distribution Date, any Rights associated with such Common Shares shall be 
deemed canceled and retired so that the Company shall not be entitled to 
exercise any Rights associated with the Common Shares which are no longer 
outstanding.

     3.   All references in the Rights Agreement to the Rights Agreement 
shall be deemed to refer to the Rights Agreement, as amended hereby.

     4.   This Amendment may be executed in any number of counterparts and 
each of such counterparts shall for all purposes be deemed to be an original, 
and all such counterparts shall together constitute but one and the same 
instrument.

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     IN WITNESS WHEREOF, the parties hereto have caused this Amendment No. 1 
to Preferred Shares Rights Agreement to be duly executed as of the day and 
year first above written.

                            METRA BIOSYSTEMS, INC.

                            By:    /S/ KURT E. AMUNDSON
                               -------------------------------------------------
                            Name:  Kurt E. Amundson
                                 -----------------------------------------------
                            Title: Chief Financial Officer
                                  ----------------------------------------------

                            THE FIRST NATIONAL BANK OF BOSTON

                            By:    /s/ KATHERINE S. ANDERSON
                               -------------------------------------------------
                            Name:  Katherine S. Anderson
                                 -----------------------------------------------
                            Title: Admin. Manager
                                  ----------------------------------------------

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