Glucagon and insulin are postulated to be physiologic regulators of hepatic biliary secretion. Effects of these hormones were studied following orthotopic transplantation. Five adult hepatic graft recipients had triple lumen t-tubes placed at the time of surgery and were studied 3 months after surgery. Experiments were performed after cholangiographic confirmation of t-tube placement and function. After overnight fast, t-tubes were inflated and bile was collected. A small quantity was saved for analysis and the remainder was reinfused to maintain enterohepatic circulation. After 1 hr of observation, the patients received a 2-hr infusion of insulin (0.125 U kg-1 hr-1), glucagon (2 micrograms kg-1 hr-1), or 0.9% saline. During saline infusions, all parameters remained stable. As has been previously demonstrated in the canine model and intact patients, bile salt outputs were constant under all experimental conditions. Glucagon stimulated bile secretion by 30% (6.7 +/- 1.5 to 8.7 +/- 1.2 ml/15 min) and inhibited biliary cholesterol output by 47% (16.4 +/- 3.2 to 8.7 +/- 1.5 mg/15 min). Bile flow and lipid secretion were not affected by insulin. Glucagon had profound effects on bile flow and lipid secretion, suggesting effects independent of innervation, while insulin at this dose had no statistically significant effects.