Local activation of procarcinogens in target tissues such as the colon by cytochrome P450-dependent microsomal monooxygenases is considered to be an important factor in the etiology of cancer. Diet and alcohol consumption are considered risk factors in colon cancer, and the cytochrome P450 isozymes CYP2E1 and CYP2C7 have been implicated in the biochemical mechanisms underlying colon cancer. The current study was conducted to determine the effects of diet and ethanol consumption on colonic and hepatic expression of these two enzymes. Adult male rat Sprague-Dawley rats were fed rat chow ad lib. or were infused intragastrically with control or ethanol-containing diets. Our results indicate that CYP2E1 is present in colonic epithelial cells, and expression of colonic and hepatic microsomal CYP2E1 and CYP2C7 was increased by chronic ethanol intake. As compared with rats having ad lib. access to standard rat food, rats receiving total enteral nutrition had significant (P < 0.01) reductions of CYP2C7 and slight, but not statistically significant, reductions in the expression of CYP2E1 in colon. Diet and ethanol differentially regulated CYP2E1 and CYP2C7 in a tissue-specific manner such that the ethanol induced CYP2E1 and CYP2C7 in the colon and liver, and the intragastric diet alone had a tendency to induce these isozymes in the liver and reduce them in the colon. These results may provide a partial explanation for the mechanism underlying effects of diet and ethanol on colon cancer.