While changes in gastric, pancreatic, and intestinal secretion in response to more recently identified gastrointestinal peptides have been characterized, there has been less investigation into effects of these hormones on hepatic bile production. The isolated perfused rat liver model has been used to examine effects of vasoactive intestinal peptide (VIP), somatostatin, bombesin, and thyrotropin-releasing hormone (TRH) on bile flow and bile acid transport. No changes were seen following bolus administration of bombesin (3 X 10(-8)-1.5 X 10(-6) M) or TRH (3 X 10(-7)-3 X 10(-6) M), while somatostatin (6 X 10(-6) M) produced a small decrease in bile flow without any change in bile acid output. VIP (3 X 10(-7) M) caused a highly significant increase in both volume of bile flow (0.85 +/- 0.8 to 1.11 +/- 0.09 microliter/min/g liver, P less than 0.001) and bile acid output (31.6 +/- 1.5 to 43.2 +/- 1.7 nmol/min/g liver, P less than 0.001). Elimination of Ca2+ from liver perfusate did not prevent VIP-induced increases in bile flow and bile acid output, and no synergistic effect of concomitant theophylline administration was observed. While effects of VIP on bile flow appear to be due to alterations in hepatic transport of bile acids, the exact mechanism(s) producing these changes remains to be elucidated.