Insulin, glucagon, somatostatin, and pancreatic polypeptide (PP) were localized in the pancreas of the common garter snake, Thamnophis sirtalis, by light and transmission electron microscopic (TEM) immunocytochemistry. Colloidal gold-protein A was used for TEM localization and the peroxidase--antiperoxidase complex technique was used for light microscopy. The glucagon-containing A cells and the insulin-positive B cells were the most numerous cell types. The somatostatin-containing D cells made up about 15% of the endocrine cells. PP-positive F cells were a minor cell type. The only topographic arrangement of the cells within the endocrine-rich areas that was apparent was the peripheral localization of the D and F cells. Cells of a specific cell type were sometimes grouped together. At the electron microscopic (EM) level, the gold particles (indicating the presence of hormone) were localized nearly exclusively over the secretory granules of the reactive cells. The alpha-granules were the largest found and were predominantly electron dense with a moderately electron-dense periphery. PP-containing granules were the smallest. The somatostatin-reactive delta-granules were round and moderately electron opaque. The beta-granules were heterogeneous in appearance. The morphognomy of the secretory granules of the major endocrine cell types is qualitatively similar to that of mammals. Whether or not the quantitative and/or associative differences contribute to the marked metabolic differences between reptiles and mammals, remains to be determined.