We have investigated the effect of bile on fat-stimulated release and basal plasma levels of cholecystokinin-33/39 (CCK) and neurotensin in six awake dogs prepared with chronic gastric and duodenal cannulas. Experimental bile diversion was achieved by catheterization of the common bile duct through the duodenal cannula; the gallbladder was undisturbed. Bile diversion significantly enhanced the release of both CCK and neurotensin that was stimulated by intraduodenal (ID) infusion of a triglyceride suspension (corn oil) (0.5 gm/kg-hr). The integrated release with ID triglyceride (ng [0 to 90 min]/ml) for CCK was control 5.58 +/- 0.83, bile diversion 14.47 +/- 2.81, bile excess 1.68 +/- 0.56, and for neurotensin was control 0.35 +/- 0.19, bile diversion 1.26 +/- 0.35, and bile excess 0.45 +/- 0.31. ID infusion of excessive bile (bile collected during bile diversion) significantly inhibited both the release and basal levels of CCK. Bile diversion alone did not modify plasma levels of CCK or neurotensin. We conclude that: endogenous bile exerts a negative feedback effect on release of CCK and neurotensin induced by triglyceride and on basal plasma levels of CCK; bile is unnecessary for the stimulation of endocrine cells in the intestinal mucosa by dietary fat; and measured basal levels of CCK and neurotensin represent a real amount of circulating peptide in the fasting state, that is, the basal levels are real and not artifactual.