The acinar distribution of ethanol-inducible cytochrome P450 was studied by immunohistochemistry using anti-rat P450 IIE1 serum. In all 17 human liver specimens staining was confined to perivenous hepatocytes. Staining was stronger in livers of alcoholics than in non-alcoholics. A similar selective perivenous staining was observed in rat liver. This pattern was exacerbated by chronic ethanol treatment, with staining appearing especially intense in hepatocytes surrounding the terminal hepatic veins. Our results demonstrate that chronic ethanol intake causes induction of P450 IIE1 in the perivenous region. We propose that this regiospecific expression and induction contributes to the perivenous damage caused by alcohol and several other hepatotoxins known to be metabolized by this enzyme.