Pancreatic islets were isolated by collagenase digestion of the pancreas from inbred Wistar rats and cultured at 20 mmol/l glucose and 5.3 mmol/l Mg++ for 4 days. About 1,000 cultured islets injected into the portal vein normalized the plasma glucose of severe diabetic rats induced by streptozotocin (45 mg/kg body weight). Spontaneous recovery of streptozotocin-treated rats was not observed in diabetic controls. Although the insulin response of transplanted rats after i.v. glucose injection (5 mmol per kg body weight) was significantly below control animals, the amount of insulin released was obviously sufficient to sustain a persisting normoglycemia of fed animals up to 1 year. The sufficient preservation of insulin content (I) and the rapid depletion of amylase content (A) of collagenase-treated pancreas fragments cultured for 48 h resulted in a significant rise in the I/A ratio. Because islet isolation is associated with islet loss, especially in the human pancreas, the short term culture enhances hopefully the possibilities for successful transplantation.