Since colchicine has been used in the treatment of alcoholic cirrhosis of the liver, the effect of this drug on ethanol metabolism in the rat has been investigated. The acute intraperitoneal injection of colchicine (500 micrograms per kg body weight) did not significantly influence in vivo ethanol elimination rate nor the ethanol peak blood concentrations following an acute dose of ethanol (3 g per kg body weight). Cytoplasmic hepatic alcohol dehydrogenase activity was not changed by in vitro colchicine. However, an approximate 30% inhibition of hepatic microsomal ethanol oxidation was observed by colchicine at a concentration of 4 microM and more. In addition, when colchicine was given chronically in a daily dose of 50 micrograms per kg body weight for 3 weeks, again in vivo ethanol disappearance from the blood was not affected by the drug. These data indicate that neither acute nor chronic colchicine administration alters in vivo ethanol elimination. But the question is raised whether colchicine can decrease hepatic acetaldehyde concentration following a therapeutic dose in vivo by inhibiting the hepatic ethanol metabolizing enzyme system. This could be a possible explanation for the observation that alcoholics improve their liver function under colchicine therapy although they continue to drink.