To study the effect of an acute dose of ethanol on carbon tetrachloride (CC14) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CC14 (1.5 ml/kg body wt.). Three hours after acute CC14 intoxication there was a striking increase in CC14 concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P<0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CC14 alone showed CC14 concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CC14 and ethanol when compared to those receiving CC14 alone, showing that ethanol given intraperitoneally or intragastrically enhances CC14 hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CC14 concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CC14, such as direct effects of ethanol on the CC14 metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CC14 hepatotoxicity by ethanol.