Indefinite survival of concordant xenogeneic Wistar Furth (WF) rat islet survival was obtained by intrahepatic transplants of cultured WF islets and a single injection of antilymphocyte sera in C57BL/6 mice. Adoptive transfer of splenocytes from mice with established WF islet xenografts produced a marked prolongation of survival of WF islets transplanted under the kidney capsule of diabetic irradiated (600 rads), naive C57BL/6 recipients(mean survival time = 48.9±17.1 days), and three of the recipients were still normoglycemic at 100 days after transplantation. Adoptive transfer of an equal mixture (3×107cells each) of these splenocytes with normal splenocytes also prolonged survival of the kidney capsule islet xenografts(mean survival time = 26.5±7.8 days vs. 15.2±5.3 days for controls). In vitro studies on lymphocyte proliferation demonstrated a low rate of proliferation of splenocytes from established islet xenografts in the presence of irradiated WF splenocytes (stimulation index = 1.6 vs. 16.2 for naive C57BL/6 mice), and mixing the cells with control splenocytes also decreased the proliferation of splenocytes as compared with controls(stimulation index = 5.4 vs. 16.2 in controls). The inhibitory effect was not species specific, since splenocytes from mice with established islet xenografts also produced a 42% inhibition of proliferation in the presence of irradiated Lewis splenocytes. These findings demonstrate that concordant, islet xenograft, immune unresponsiveness can be adoptively transferred by splencotyes from mice with established islet xenografts.