Isolated hamster islets were 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°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°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 normogly-cemia 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 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. © 1987 by The Williams & Wilkins Co.