CBA/H (H-2k) male mice were made diabetic by giving Streptozotocin 300 mg/kg intravenously. They were transplanted beneath the renal capsule with seven clusters of BALB/c (H-2d) adult islets, cultured for seven days in 95% O2 and 5% CO2. Basal blood glucose and weight gain returned to normal within 7 to 10 days. Blood glucose and serum insulin responses to intragastric glucose, intraperitoneal arginine and intraperitoneal theophylline were assessed after restoration of normoglycemia and compared with the responses in a control group of CBA mice. The animals were pretreated with intraperitoneal phentolamine and propranolol to reduce the stress of these procedures. Essentially normal carbohydrate tolerance was maintained in the transplanted animals but the insulin responses were markedly reduced, suggesting an increased sensitivity to insulin. The insulin content of the grafted tissue was also found to be considerably lower than that in the normal pancreas. This study demonstrates that in the mouse, adult pancreatic islet allografts can respond to stimuli that require functional adaptation by the islets. Further studies are required in larger animals before islet transplantation can be applied to the management of insulin dependent diabetic patients.