The mechanism by which alcohol causes pancreatic damage is still largely unknown. One important contributory factor may be the endothelins, potent vasoconstricting endothelial-derived peptides. The aim of this study was to examine in vivo endothelin release from the pancreatic vascular endothelium after alcohol ingestion. In anesthetized cats immunoreactive endothelin was measured in serum after instillation of alcohol into the stomach (20 ml, 40%). After intragastric alcohol, a rise in endothelin was seen in pancreatic venous effluent (to a mean of 24.5 +/- 7.7 pg/ml at 60 min). Control serum from the femoral artery exhibited no rise in endothelin (2.11 +/- 1.2 pg/ml). Pancreatic blood flow was significantly decreased in a further group to 93% basal after intravenous infusion of 0.1 nmol/kg ET-1 and to 61% after infusion of 1 nmol/kg ET-1. Portal serum levels of endothelin were 105 pg/ml and 15 pg/ml, respectively, immediately following bolus infusion and decreased to normal levels within 120 sec. We conclude that the serum endothelin rise after intragastric ethanol may be a major factor behind the drop in pancreatic blood flow.