We reported previously that dietary proteins stimulate pancreatic secretion by a mechanism not involved in masking trypsin activity in rats that have bile-pancreatic juice (BPJ) diverted from the proximal small intestine for 7 days. However, BPJ in the distal small intestine is possibly responsible for the stimulation of pancreatic secretion in chronic BPJ- diverted rats. To examine whether the BPJ-dependent mechanism operates in the distal small intestine of chronic BPJ- diverted rats, we investigated pancreatic responses after inhibition or removal of pancreatic trypsin activity in the distal small intestine of conscious rats. Duodenal instillation of soybean trypsin inhibitor (SBTI), which is a proteinaceous trypsin inhibitor, stimulated pancreatic secretion in the chronic BPJ-diverted rats, whereas a nonpeptidic trypsin inhibitor, FOY 305, did not. Heal administration of both trypsin inhibitors did not enhance pancreatic secretion in the diverted rats. Exclusion of luminal BPJ from the distal small intestine was also ineffective in causing pancreatic exocrine secretion in the chronic BPJ-diverted rats. These observations reveal that ileal BPJ does not contribute to the stimulation of pancreatic secretion in rats that have BPJ chronically diverted into the ileum, as in intact rats, and that a duodenal instillation of SBTI stimulates pancreatic secretion as a protein, and not as a trypsin inhibitor.