Adult rats were partially depancreatized, and approximately 500 islets were isolated from each excised pancreas, maintained in tissue culture for 7 days, and subsequently transplanted back to the same animals beneath the renal capsule. Four weeks after transplantation the animals were anesthetized and given an intravenous injection of 1 ml of either saline, 30% (wt/vol) D-glucose, 30% (wt/vol) D-galactose, DL-propranolol (15 mg/kg body wt) dissolved in saline, or terbutaline (1 mg/kg body wt) dissolved in saline. Five minutes later blood perfusion of the islet grafts and the pancreatic remnant were measured with a microsphere technique. Islet blood flow was also measured in animals with pancreas intact and no islet grafts after administration of saline, glucose, or galactose. These animals demonstrated a significant and preferential increase in islet blood flow after glucose administration, whereas galactose caused a selective decrease in islet blood perfusion. Both whole pancreatic blood flow and islet blood flow in the pancreatic remnant were decreased by terbutaline administration, whereas the other substances had no effect. Blood flow to the transplanted islets was decreased by glucose and galactose, whereas propranolol and terbutaline had no effect compared with the saline-injected animals. These results suggest that blood flow regulation differs between transplanted pancreatic islets, islets in the normal pancreas, and islets in the pancreatic remnant after partial pancreatectomy. Whether this reflects lack of innervation or an altered reactivity of the newly formed blood vessels in islet grafts is presently unknown.