The importance of peptic digestion of dietary protein in pancreatic enzyme secretion and cholecystokinin (CCK) release was investigated in conscious rats. Native casein and native bovine serum albumin (BSA) were infused intragastrically and intra-intestinally, and the effect of peptic predigestion on the pancreatic secretory and plasma CCK responses to BSA were determined (all infused at 450 mg/h). When dietary proteins were infused intraduodenally, native casein was a much stronger stimulant of CCK release (5.8 +/- 0.6 vs. 1.6 +/- 0.2 pM) and pancreatic protein secretion [5,592 +/- 736 vs. 750 +/- 461 (0-180)mg.kg-1.min] than native BSA. Infusion by the intragastric route markedly increased pancreatic protein secretion for BSA but not for casein. HCl-pepsin treatment of BSA significantly increased its ability to increase pancreatic secretion and plasma CCK. Pancreatic protease binding to native BSA was inferior compared with casein. Peptic digestion of BSA increased its protease binding activity more than threefold. The results indicate that peptic digestion of dietary proteins enhances the proteins' ability to elicit the pancreatic feedback stimulatory response.