Induction of cytochrome P450 CYP 2E1 during chronic ethanol exposure in rats has been reported by our laboratory to occur by a complex two step process. The first step occurs at relatively low blood alcohol concentrations and involves increases in CYP 2E1-dependent activities and apoprotein levels with no increases in steady-state mRNA encoding CYP 2E1. The second step of this process occurs at higher blood alcohol concentrations and involves elevated mRNA levels. In this report, we demonstrate for the first time that CYP 2E1 induction by chronic ethanol is associated with increased CYP 2E1 gene transcription and is independent of gonadal factors.