This study was undertaken to delineate the role of cholecystokinin (CCK) in bombesin- and meal-stimulated pancreatic polypeptide (PP) secretion in seven conscious dogs by studying: (1) the stimulatory effect of similar plasma levels of CCK induced by a meal and infusions of bombesin and the synthetic CCK analog cerulein on plasma PP, and (2) the inhibition of PP secretion by the CCK-receptor antagonist CR-1409 during these three stimuli. The stimulation of PP secretion during bombesin (11.0 +/- 1.6 nM/hr) and after the meal (8.9 +/- 2.0 nM/hr) were significantly (P less than 0.05) greater than during infusion of the CCK analog cerulein (2.7 +/- 0.4 nM/hr). CR-1409 significantly inhibited the bombesin- and meal-stimulated PP secretion to 2.0 +/- 0.4 nM/hr (81%; P less than 0.05) and 3.1 +/- 1.2 nM/hr (47%; P less than 0.05), respectively, while the cerulein-stimulated PP release was almost abolished to 0.2 +/- 0.1 nM/hr (93%; P less than 0.05) by the drug. These findings point to an important role for CCK in the regulation of bombesin- and meal-stimulated PP secretion.