Survival of highly immunogenic hamster islet xenografts can be achieved in rats if the graft is transplanted into the abdominal testis. Permanent survival requires the administration of cyclosporine during the first thirty days after grafting. The majority of grafts will survive indefinitely beyond this point if the grafted animals receive a once-weekly maintenance dose of CsA until day 100, when CsA is no longer necessary. Hamster islet xenografts transplanted under the kidney capsule or into the portal vein are rejected, regardless of CsA treatment. Animals maintaining long-term primary intratesticular xenografts accept secondary contralateral testicular xenografts. CsA is not required. Primary grafts are also resistant to the adoptive transfer of lymphocytes from rat donors primed to hamster xenoantigens. Secondary hepatic and renal islet xenograft survival is also extended--some hepatic grafts long-term. Therefore, the combination of CsA and the privileged status of the abdominal testis leads not only to the acceptance of primary intratesticular islet xenografts but also to partial immunological unresponsiveness of subsequent grafts in other sites.