Blood flow to the pancreatic islets of the rat was estimated with the microsphere technique. Experiments with microspheres of different sizes (diameter 10, 15 or 50 micron) showed that optimal results were obtained with 10-micron spheres. Localization of microspheres either within or outside the islets was accomplished by freeze-thawing of the pancreas, making it transparent, so that both islets and microspheres could be distinguished in dark field illumination. Thus, microscopic examination of the freeze-thawed pancreas allowed the microspheres to be counted separately in both the endocrine and exocrine parenchyma. Under basal conditions, pancreatic blood flow was calculated as 0.60 ml X min-1 X g-1 (w/w). The islets accounted for about 10% of the total pancreatic blood flow, corresponding to 0.069 ml/min per whole pancreas. A bolus dose of glucose increased pancreatic blood flow to 0.75 ml X min-1 X g-1 (p less than 0.05), while the fractional islet blood flow rose to 15.1% (p less than 0.001) corresponding to 0.125 ml X min-1 X pancreas-1 (p less than 0.001). The glucose-induced increase in pancreatic blood flow mainly resulted from increased flow to the pancreatic tail, while the corresponding increase in islet blood flow was uniformly distributed throughout the pancreas. Injection of the non-metabolizable glucose-derivate. 3-0-methyl-D-glucose, affected neither the pancreatic nor the islet blood flow. The data indicate that the islets receive more of the pancreatic blood flow than would be accounted for by their relative volume and that glucose preferentially stimulates blood flow to the islets.