A single injection of streptozotocin into mice produced an extensive necrosis of the beta cells resulting in permanent diabetes. The histological changes in the islets were similar to those described after the injection of alloxan. The regenerative capacity of beta cells which survived the cytotoxic injury was limited. Hypoglycemia induced by an injection of insulin or hyperglycemia induced by glucose injections sensitized the beta cells to streptozotocin. In contrast, injection of insulin antibody effectively protected the beta cells from the cytotoxic injury. Streptozotocin caused widespread necrosis of the beta cells of the guinea pig and the obese hyperglycemic mouse. Both these species had proven resistant to the diabetogenic effect of alloxan. Diabetic guinea pigs were observed for eight months, without reversion of the diabetic syndrome.