The aim of the study was to evaluate whether intestinal glucoreceptors participate in the regulation of pancreatic islet blood flow. For this purpose, anesthetized rats were infused (0.1 ml/min for 3 min) with saline, glucose, or 3-O-methylglucose directly into the duodenum. The glucose (1 mg/kg body wt) infusion rate was chosen to prevent any effects on systemic or intraportal blood glucose concentrations. Intraduodenal infusion of D-glucose increased both serum insulin concentration and islet blood flow, whereas the osmotic control substance 3-O-methylglucose had no such effects. A bilateral abdominal vagotomy performed before the infusions totally abolished both the insulin and blood flow response to glucose infusion. The absence of an increased islet blood flow in response to glucose infusion in the denervated, transplanted pancreas was a further indication of the crucial importance of the regulation of islet blood flow by the vagus nerves. It is concluded that intestinal glucoreceptors participate in the mediation of glucose-induced islet blood flow increase.