Pancreatic islet cells containing both glucagon and pancreatic polypeptide simultaneously (glucagon/PP cells) were identified in the rat and human normal pancreas using immunocy-tochemical staining on consecutive serial sections and double-immunolabeling techniques on the same sections. Numerous glucagon/PP cells were found at the periphery of the islets in all regions of the pancreas, particularly in the rat. As a whole, these bipeptide-containing cells appeared in higher proportions than the cells secreting glucagon or PP separately. Double immunogold labeling performed on both surfaces of the thin tissue sections allowed differentiation between the glucagon/PP cells and the single-labeled glucagon or PP cells at the ultra-structural level. The pancreatic glucagon/PP cells displayed the morphological characteristics of either A cells or PP cells. Both peptides were found in the same secretory granules of the glucagon/PP cells and, in the human pancreas, the glucagon/PP cells displayed secretory granules with a dense core in which both peptides were rather concentrated. The coexistence of glucagon and PP is assumed to originate from the simultaneous expression of the two different genes in the same cell and suggests that the cellular processing through the rough en-doplasmic reticulum-Golgi apparatusgranule secretory pathway for both peptides takes place in parallel.