PYY is a neurohormonal peptide structurally related to neuropeptide Y (NPY) and pancreatic polypeptide (PP). PYY, NPY and PP are all 36-amino acid peptides with C-terminal amide structure. PYY-immunoreactive (PYY-IR) material has been demonstrated both in gastroentero-pancreatic endocrine cells and in neurons in the,out wall, suggesting that PYY is a peptide with a widespread distribution, and with a dual occurrence in neurons and endocrine cells. In the intestinal endocrine cells, where the bulk of PYY in the body is located, the PYY-IR material coexists with glucagon (glicentin). In the stomach, immunoreactive PYY occurs in antral gastrin cells, and in some fundic somatostatin cells. In the endocrine pancreas, coexistence with both glucagon (mouse, rat) and with PP (cat, dog, pig) has been demonstrated. The occurrence of authentic PYY in the pancreas is supported by the finding of PYY mRNA. Interestingly the mRNA abundance in the rat pancreas peaks early postnatally. PYY-IR material is present also in intramural neurons in the stomach and uppergut. In cat, ferret, and pig PYY-IR nerve fibers are abundant in the myenteric ganglia and in the circular smooth muscle, but rare or absent in the submucosa and the muscularis mucosae. In some species, such as the mouse and rat, PYY-IR nerves are restricted to the minor side of the stomach. Combined HPLC and RIA analysis suggests that the PYY-IR material in neurons is identical with authentic PYY, and distinct from NPY. These data emphasize a role for PYY as a neuropeptide in the gut, in addition to its role as a messenger in endocrine/paracrine cells.