A new model is proposed for pancreatic enzyme secretion in response to food protein intake in rats. We have found a novel peptide in rat bile-pancreatic juice, which exhibits a trypsin-sensitive, cholecystokinin (CCK)-releasing activity. The amino acid sequence of the peptide purified from rat bile-pancreatic juice is very similar to that of a conservative region in pancreatic secretory trypsin inhibitor (PSTI). The peptide loses its CCKreleasing activity during trypsin digestion, but food protein intake prevents this trypsin digestion. Results of a reconstitution experiment indicate that pancreatic enzyme secretion in respoqse to food protein intake only occurs as a result of interaction between trypsin and our purified peptide. Also, a peptidespecific antibody abolished the response. These findings lead us to hypothesize that this peptide acts as an intraduodenal mediator for CCK release in response to food protein intake.