This study was designed to investigate the changes in plasma and tissue endothelin-Uendothelin-2 (ET) after liver ischemia and to assess the protective effect of anti-ET 1/ET 2 monoclonal antibody (ET antibody) against ischemia-reperfusion injury. The ET levels in the liver tissue, hepatic venous blood of the ischemic and nonischemic sides, and in the portal venous blood were measured before and after partial liver ischemia for l hour in the adult dog. The ET levels in the liver tissue and hepatic venous blood on the ischemic side increased slightly during ischemia and markedly after reperfusion, whereas those on the nonischemic side showed no significant increases. The ET levels in the portal venous blood peaked at 1 to 3 hours after ischemia, which was significantly higher than the levels in the hepatic venous blood on the ischemic side and which correlated with the portal venous pressure elevated because of the partial liver clamping. The administration of antibody (2 mg/kg, intravenous) before reperfusion resulted in a significant inhibition of the postreperfusion elevations of serum-glutamic-oxaloacetic transaminase (GOT), S-glutamic pyruvic transaminase (GPT), and the indocyanine green (ICG) dye retention rate. In conclusion, ET was produced both in the liver tissue exposed to ischemia and in the vascular endothelium of the portal bed exposed to portal congestion. The ET released from the vascular endothelium, including the liver and the portal bed, was found to be a possible factor of ischemia-reperfusion injury. (HEPATOLOGY 1995;21:1138-1143.) A number of vasoactive substances produced in the endothelial cells have been identified.'" One of the vasoconstrictive substances is endothelin (ET), a strongly vasoconstrictive peptide that was isolated from the culture supernatant of vascular endothelial cells and for which the structure was determined in 1988 by Yanagisawa et al.3 It has drawn much attention as a vasoconstrictor-peptide and as a substance closely related to Abbreviations: ET, endothelin; Ig, immunoglobulin; ICG, indocyanine green; GOT, glutamic-oxaloacetic transaminase; GPT, glutamic pyruvic transaminase.