We demonstrated specific binding of the insulin-releasing hormone glucagonlike peptide (GLP)-I-(7-36)-amide, an intestinal product of proglucagon, to pancreatic islet cells by autoradiography using 125I-labeled GLP-I-(7-36)-amide incubated with tissue specimens of extracerebral rat organs. We also found binding of 125I-GLP-I to insulin-, glucagon-, and somatostatin-immunoreactive cells by combined autoradiographic and immunohistochemical analysis of pancreatic specimens using antisera against insulin, glucagon, and somatostatin. An accumulation of radioactivity was also observed in the stomach surface epithelium but could not be prevented by excess unlabeled peptide. No binding was found in other tissues investigated, including the lungs and the small intestinal mucosa. Localization of the binding sites identifies the pancreatic islets as the prime target for GLP-I-(7-36)-amide and suggests that it exerts direct effects on islet cells.