The role of cholecystokinin in bombesin-stimulated pancreatic secretion in dogs was examined by the use of a specific cholecystokinin antagonist, proglumide. The primary component of bombesin-stimulated pancreatic secretion at the lowest tested dose was due to cholecystokinin, with only 25 percent of bombesin-stimulated protein output preserved during proglumide infusion. Maximal stimulation of cholecystokinin release was achieved by even the lowest dose of bombesin, whereas dose-related increases in bombesin-stimulated protein secretion were observed. This increase in exocrine secretion is probably explained by increased direct bombesin stimulation. Our findings suggest that the maximal dose of bombesin is lower for cholecystokinin release than its effective dose for enzyme secretion. We conclude that, in all probability, postprandial release of bombesin (or its analogue, gastrin-releasing peptide) affects pancreatic function primarily through release of cholecystokinin.