Exocrine pancreatic secretion is under partial control of endocrine pancreatic hormones. We studied the interaction of three doses of acetylcholine (Ach), a stimulator of exocrine and endocrine pancreatic secretion, with one dose of gastric inhibitory polypeptide (GIP) which is strongly insulinotropic, but has no effect on exocrine pancreatic secretion. The effects of Ach and GIP on insulin secretion from the rat pancreas were additive at 0.05 X 10(-6) M Ach and slightly, but not significantly less than additive at 0.25 or 2.5 X 10(-6) M Ach. GIP had an augmenting effect on amylase and volume secretion from the pancreas, when pancreatic secretion was stimulated by 2.5 X 10(-6) M Ach, but not by 0.05 or 0.25 X 10(-6) M. Exogenous rat insulin could exert an effect similar to that of GIP, although a higher dose was required. Atropine inhibited the effect of Ach on exocrine and endocrine pancreatic secretion, but not the insulinotropic action of GIP. It is hypothesized that GIP could play a role in regulating exocrine pancreatic secretion by its insulinotropic action.