Rat liver microsomes were prepared from male and female controls and from animals pretreated for 3 weeks with ethanol, and incubated with dimethylnitrosamine (DMN) and an NADPH-regenerating system. The formation of formaldehyde and nitrite as well as the alkylation of microsomal protein were found to be greatly enhanced, especially in the low DMN concentration range, as a result of long-term ethanol induction. In contrast, ethanol or tetrahydrofuran, when incubated simultaneously with DMN, inhibited microsomal metabolism of the carcinogen.