The purpose of this study was to analyze changes in plasma endothelin-1 levels during hemorrhagic shock. Thirty-two mongrel dogs were divided into four equal groups with group I as the controls and groups II through IV as experimental groups. The dogs in the experimental groups underwent hemorrhagic procedures. The mean blood pressure was kept at the level of 65 mm Hg in group II, 50 mm Hg in group III, and 40 mm Hg in group IV. Blood samples were collected from each dog under the following conditions: (1) after induction of anesthesia, when the animals were hemodynamically stable, before the start of shock; (2) 1 minute after the mean arterial pressure dropped to the level designed for each group (shock 1); (3) 15 minutes after shock 1; (4) 30 minutes after shock 1; (5) 1 hour after shock 1; (6) 2 hours after shock 1; (7) 4 hours after shock 1; and (8) 8 hours after shock 1. Plasma endothelin-1 levels both in arterial and venous blood were analyzed in each dog. The results showed that (1) arterial endothelin-1 concentrations were considerably lower than venous concentrations at the baseline level; (2) after the shock-1 point; plasma endothelin-1 concentrations increased, first markedly and then evenly throughout the oligemic period; (3) elevation of plasma endothelin-1 levels was significantly linearly correlated with the amount of blood loss at the time of 2 hours after shock and thereafter; (4) the arterial/venous ratio of plasma endothelin-1 levels during the oligemic period was higher than that in the control group. The elevation of plasma endothelin-1 concentrations during hemorrhagic shock is a combined result of the activation of stress hormones and the coagulation cascade and the decrease of blood flow in the kidneys and the lungs. The arteriovenous differences in plasma endothelin-1 levels during the oligemic period occur as a result of decreases in pulmonary and renal clearance, and the hypersecretion of endothelin-1 from vascular endothelial cells. Since endothelin-1 can exert vasconstrictive as well as a direct inotropic effect on the myocardium, it is postulated that endothelin released during hemorrhagic shock functions as a reactive substance and plays an important role in maintaining the vascular tonus and the perfusion pressure of the vital organs.