To elucidate possible causes of the hepatocyte swelling and necrosis found in alcoholic liver disease, the effects of ethanol and acetaldehyde on the activities of two hepatic plasma membrane ATPases--(Na+K+) ATPase and Mg2+ ATPase--were investigated. The activity of another plasma membrane-bound enzyme, 5' nucleotidase, was also determined to assess the specificity of these effects. Over concentrations ranging from 8 to 90 mM ethanol did not cause significant inhibition of any of the three enzymes. At 120 mM ethanol (Na+K+) ATPase activity was inhibited by 20% (P less than 0.01) and at higher concentrations there was progressive inhibition of all three enzymes that was non-competitive in type. Acetaldehyde produced non-competitive inhibition of (Na+K+) ATPase and Mg2+ ATPase at concentrations of 6 and 56 mM respectively and 5' nucleotidase activity was also inhibited at these concentrations. We conclude that ethanol and acetaldehyde inhibit (Na+K+) ATPase and Mg2+ ATPase activities as part of a generalised effect on the liver plasma membrane. Because the inhibitory concentrations of both substances are higher than are usually found in alcoholic subjects or in experimental animals after alcohol feeding, it seems unlikely that direct suppression of ATPase activity by ethanol or acetaldehyde is responsible for the morphological abnormalities of alcohol-induced liver disease. It could, however, be implicated in the development of hepatocellular necrosis in severe ethanol poisoning.