Tritiated glibenclamide binds to specific receptors and is internalized in pancreatic insulin-producing B-cells. We investigated, therefore, whether tritiated glibenclamide could be used to preferentially label the endocrine, as distinct from exocrine, pancreas. In isolated rat pancreatic islets, the net uptake of ³H-glibenclamide reached within 30 min of incubation a near-equilibrium value, corresponding to an apparent distribution space close to three to four times the islet volume. In pieces of pancreas exposed up to 1 h to ³H-glibenclamide, however, its apparent distribution space progressively increased and, even at the min 60 of incubation, did not exceed a third of the wet weight of the pieces. Yet, no significant difference could be detected between the time course for ³H-glibenclamide uptake by pancreatic pieces from either control animals or rats injected with streptozotocin a few days before the experiments. Likewise, no significant difference in the paired ratio between the radioactive content of the pancreas and plasma could be found between the control and diabetic rats when examined 1, 5, or 24 h after the IV administration of ³H-glibenclamide. These findings indicate that the sulfonylurea does not represent a suitable tool for preferential labeling of the endocrine pancreas in the perspective of its imaging by a noninvasive procedure.