The objective of the present study was to clarify the differential effects of endothelinA (ETA) and ETB antagonism in the early phase of ischemia-reperfusion damage. Male Sprague Dawley rats were randomly divided into 4 groups: control (n = 10), bosentan (40 nM; n = 10), BQ-485 (20 nM; n = 10), and BQ-788 (50 nM; n = 10) to compare the effects of ETA or ETB or both ETA and ETB antagonists against the warm ischemia-reperfusion damage of murine livers. Isolated livers were perfused with oxygenated Krebs-Henseleit bicarbonate buffer solution and ET antagonists for 30 min before inducing warm ischemia (non-recirculating system). After 40 min without perfusate, measurements (portal pressure, O2 tensions of influent and effluent perfusate, liver enzymes, etc.) were taken up to 60 min after reperfusion. The BQ-788 group had significantly more liver damage than did the other groups, and more O2 consumption than did the bosentan group. BQ-485 and bosentan were more protective at some points after reperfusion. Antagonism of only the ETB receptors is detrimental, but antagonism of the ETA receptors appears to have a role in protecting the liver from warm ischemia-reperfusion damage in the early phase.