In the perfused rat liver, infusion of ethanol induced an initial increase in portal pressure which is an indicator of vasoconstriction and a subsequent increase in lactic dehydrogenase (LDH) release, which is an indicator of cell damage in a dose-dependent fashion. Simultaneous infusion of sodium nitroprusside, a potent vasodilator, (100 microM) inhibited the increases in portal pressure and LDH release. Focal hepatocellular necrosis evidenced by trypan-blue stained cell nuclei were localized in midzonal and pericentral area of the liver lobules at 60 min after ethanol load. These ethanol-induced microcirculatory disturbance might be involved in the pathogenesis of alcoholic liver disease.