Isolated hamster islets wre transplanted either into the liver via the portal vein or into the renal subcapsular space of diabetic C57BL/6J mice. The mean survival time (MST) of hamster islets cultured overnight at 37.degree. C was 8.5 .+-. 0.6 days when transplanted into the liver as compared to an MST of > 21.7 .+-. 4.9 days with 1 recipient still normoglycemic at 60 days when the islets were placed in the renal subcapsular space. Low-temperature culture (24.degree. C) of the hamster islets for 7 days produced a further significant prolongation of xenograft survival when the islets were placed beneath the renal capsule (MST > 43.3 .+-. 4.7 days) with 2 recipients normoglycemic at 60 days. A single injection of anti-T-lymphocyte serum in conjunction with low-temperature culture did not produce a further increase in MST; however, 3 recipients were normoglycemic at 60 days. Removal of the kidney bearing successful xenografts at 60 days resulted in a rapid return to the diabetic state. It was interesting that the xenografts maintained normoglycemia in the mice at a level equivalent to the normal hamster (66.2 .+-. 4.7 mg/dl) instead of the nonfasting level found in normal C57BL/6J mice (128.4 .+-. 6.4 mg/dl). The findings indicate that low-temperature culture of the donor islets in conjunction with using the renal capsule as the site of the transplantation produced a marked prolongation of hamster islet xenograft survival. Slow rejection of the xenografts did occur in this site, and histologic studies indicated that this rejection may be antibody mediated.