Both glucagon and prostaglandin F2 alpha have been shown to stimulate a chloride-rich choleresis in dogs. This study was performed to ascertain the interrelationship between glucagon and prostaglandin F2 alpha in stimulating bile flow. The experiments were performed using dogs with chronic biliary and gastric fistulas. Initially, the effects of prostaglandin F2 alpha on serum glucagon levels were evaluated. Glucagon administration increased bile volume and chloride secretion as did prostaglandin F2 alpha. Serum glucagon levels during prostaglandin F2 alpha administration were increased significantly over baseline values. During prostaglandin F2 alpha administration, the increase in serum glucagon concentration correlated well with the increase in hepatic bile flow. Administration of somatostatin, a hormone known to inhibit glucagon release, prevented the choleresis produced by prostaglandin F2 alpha while simultaneously eliminating the hyperglucagonemia. Subsequently, the effects of glucagon on bile prostaglandin F secretion and the effect of prostaglandin synthetase inhibition on glucagon choleresis were evaluated. Bile prostaglandin F secretion increased from control values of 101 +/- 27 pg per min (mean +/- S.D.) during bile salt infusion alone to 1,498 +/- 1,086 pg per min during the administration of 1 microgram kg-1 hr-1 glucagon. The prostaglandin synthetase inhibitor, indomethacin, significantly decreased the choleresis, the increased bile chloride secretion and the increased bile prostaglandin F secretion produced by glucagon. The results of this study indicate that prostaglandin F2 alpha-stimulated bile flow is primarily the result of glucagon release and suggest that prostaglandin F2 alpha may be involved in glucagon secretion.(ABSTRACT TRUNCATED AT 250 WORDS)