The influence of the intestinal bile acid content on the secretion of the exocrine pancreas and on the plasma concentrations of the relevant peptides (NT), and CCK is the subject of continuing controversy. Thus the alterations of pancreatic secretion and both hormones during variations of intestinal bile acid content were investigated. Modified Herrera fistulas were implanted in six dogs for analysis of the pancreatic secretions. Intraduodenal application of taurocholate (1.8, 3.6, or 7.2 mM) led to a marked reduction of the pancreatic secretion as well as to a simultaneous decrease of NT and CCK release after stimulation by the intraduodenal instillation of a 20% lipid emulsion. (The integrated protein secretion decreased from 20.1 +/- 1.9 g to 15.2 +/- 1.6 g, NT release dropped from 4970 to 3050 pg/180 min, and CCK from min.) cholestyramine together with the lipid emulsion had the opposite effect. The pancreatic protein as well as NT and CCK release increased. It therefore appears that there is a negative feedback relationship between the postprandial intestinal bile acid content on the one hand, and the secretion of the exocrine pancreas and the regulatory peptides NT and CCK on the other hand. This relationship is independent of any interaction between pancreatic proteases and bile acids.