The role of intestinal luminal bile on cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) release was examined in dogs with chronic external bile diversion. In 6 mongrel dogs, cholecysto-jejuno-cystostomy (C-J-C) was performed using a small segment of the middle small intestine interposed between the gallbladder and urinary bladder with section of the common bile duct. Butter dissolved in 30 ml of lukewarm water was orally ingested before surgery, and same amount of butter solution with or without graded volumes of canine bile were orally ingested between four to six weeks after C-J-C surgery. Increases in both plasma triglyceride and GIP levels after butter ingestion were almost completely abolished by C-J-C, but they were restored by oral bile feeding in a volume-dependent manner. Both basal and fat-stimulated CCK release were enhanced significantly by C-J-C, and oral bile feeding inhibited fat-stimulated CCK release by bile in a dose dependent manner. These data suggest that intraluminal bile regulates basal and fat-stimulated CCK release and fat-stimulated GIP release in dogs.