The effect of chronic ethanol administration on 1,2-dimethylhydrazine induced rectal carcinogenesis was investigated in 32 paired male Sprague-Dawley rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02), whereas no cocarcinogenic effect of ethanol was observed in other parts of the intestine. Alcohol did not influence tumor size or histopathology. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol fed and pair fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol mg protein-1 hr-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.