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                                                               Exhibit No. 10.65


Mr. E. Andrews Grinstead
33 Edgehill Road
Brookline, MA  02446

Dear Andy:

         This letter sets forth the terms we have agreed upon with respect to
your termination of employment from Hybridon, Inc. ("Hybridon" or the
"Company"). This letter agreement ("Agreement") is effective seven (7) days
after it has been signed by each of us (the "Effective Date"). We agree as
follows:

         1. Your employment with the Company shall be deemed to have terminated
as of April 30, 2000 (the "Termination Date"), and you shall accrue service time
for all purposes with the Company through the Termination Date, including
vesting of options.

         2. Your termination shall be deemed to be a termination because of a
disability and you shall be entitled to all rights and benefits accruing to you
as a result of such termination under your 1997 Employment Agreement and under
all other agreements related to your employment.

         3. Because your termination is a result of a disability, in accordance
with your 1997 Employment Agreement, you shall have until two years after the
Termination Date to exercise all Hybridon stock options that are fully vested as
of the Termination Date.

         4. As of the Termination Date, you had an outstanding note with
Hybridon totaling $273,850 (the "Note"). As of the Termination Date, the note
will be forgiven and no further payments of either principal or interest shall
be due thereunder.

         5. You shall be eligible for distribution of retirement benefits in
accordance with the terms of the Hybridon plan and you shall receive all
benefits that are provided to you under the various Hybridon employee benefit
plans, in accordance with their respective terms except as modified by the 1997
Employment Agreement. Hybridon shall pay the cost of the monthly premium for you
and your family for the duration of the group health insurance COBRA
continuation coverage period. You are eligible for payment of benefits under the
Hybridon long-term disability insurance plan. The Company will assist you by
using its best reasonable efforts to ensure that the long-term disability
benefit is paid to you in accordance with its terms.

         6. Hybridon shall pay your reasonable attorney's fees with respect to
advice and counsel you have received to your termination of employment, up to
$10,000.


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         7. By signing below, you acknowledge and agree that the consideration
contained herein and in Paragraphs 4, 5 and 6 in particular, represents full and
complete consideration for your release of claims pursuant to Paragraph 8 below.

         8. Pursuant to this Agreement you shall be deemed to have resigned as
an officer and Director of the Company as of the close of business on the
Effective Date.

         9. (a) You, on behalf of yourself, and your heirs, family members,
executors, administrators and assigns, hereby fully and forever release the
Company and its members, managers, officers, employees, directors, successors,
and assigns (the "Releasees"), from any claim, duty, obligation or cause of
action relating to your employment by the Company, whether presently known or
unknown, suspected or unsuspected, that you may possess arising from any
omission, acts or facts that have occurred up until and including the Effective
Date including, without limitation:

-        any and all claims relating to your employment relationship with the
         Company and the termination of that relationship;

-        any and all claims for wrongful discharge of employment, breach of
         contract, both express and implied; breach of a covenant of good faith
         and fair dealing, both express and implied, negligent or intentional
         infliction of emotional distress; negligent or intentional
         misrepresentation; negligent or intentional interference with contract
         or prospective economic advantage; defamation; negligence; personal
         injury; assault, battery; invasion of privacy; false imprisonment, and
         conversation; and

-        any and all claims for violation of any federal, state or municipal
         statute, including, but not limited to, Title VII of the Civil Rights
         Act of 1964, the Civil Rights Act of 1991, the Age Discrimination in
         Employment Act of 1967, the Americans with Disabilities Act of 1990,
         the Family and Medical Leave Act, the Fair Labor Standards Act, M.G.L.
         c .151B, and The Massachusetts Fair Employment Practices Act, M.G.L. c
         151B.

         You agree that the release set forth in this Paragraph shall be and
remain in effect in all respects as a complete general release as to the matters
released. This release does not extend to any obligations incurred under this
Agreement, nor does it extend to any claims you may have as a shareholder,
option holder or holder of a note or other form of security of the Company,
whether such claims relate to an event or omission occurring before or after the
Effective Dated.


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                  (b) The Releases hereby irrevocably and unconditionally
release, acquit and forever discharges you, your spouse, heirs and successors
from any claim, duty, obligation or cause of action relating to your employment
by the Company, whether presently known or unknown, suspected or unsuspected,
that they or each of them may possess arising from any omissions, acts or facts
that have occurred up until and including the Effective Date including, without
limitation, all charges, complaints, claims, liabilities, obligations, promises,
agreements, controversies, damages, actions, causes of actions, suits, rights,
demands, costs, losses, damages and expenses (including attorney's fees and
costs actually incurred) of any nature whatsoever known or unknown, suspected or
unsuspected.

         10. You acknowledge that you are waiving and releasing any rights you
may have against the Company, including claims under the Age Discrimination in
Employment Act ("ADEA"), as of the Effective Date. You acknowledge that the
consideration given for this waiver and release Agreement is in addition to
anything of value to which you are already entitled. You further acknowledge
that you have been advised by this writing and understand and agree that:

         -        you have been advised to consult with an attorney prior to
                  executing this Agreement;

         -        you have carefully read and fully understand this Agreement;

         -        you are, through this Agreement, releasing the Company and the
                  Releasees referenced in 9(a) above, from any and all claims
                  you may have against it and them, as described herein;

         -        you knowingly and voluntarily agree to all of the terms set
                  forth in this Agreement;

         -        you have had at least twenty-one (21) days within which to
                  consider this Agreement;

         -        you have seven (7) days following the execution of this
                  Agreement by the Parties to revoke the Agreement; and

         -        this Agreement shall not be effective until the revocation
                  period has expired.

         By your signature below, you acknowledge that you have read and
understood the terms of this Agreement, and that you are signing it voluntarily
and without coercion. You and the Company further acknowledge that the

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mutual release waivers contained in this Agreement are knowing, conscious and
made with full appreciation that each is forever foreclosed from pursuing any of
the rights so waived. The undersigned represents and warrants that he has
authority from the Company to enter into this Agreement.

ACKNOWLEDGED AND AGREED:

Dated:                     , 2000
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                                                 E. Andrews Grinstead, III


                                                         HYBRIDON, INC.
Dated:                     , 2000                By:
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