The hepatic microsomal metabolism of cocaine and the pharmacological effects of some metabolites were studied in experimental animals. Hepatic microsomes from mice, rats and guinea pigs catalyzed the oxidation of cocaine to m- and p-hydroxycocaines. Only trace amounts of m-hydroxycocaine were detected in the extract of the incubation mixture with rabbit hepatic microsomes. The total amount of the two hydroxycocaines was less than 12% that of norcocaine which was the most predominant microsomal metabolite in all the animals species examined. The administration of p-hydroxycocaine (20 mg/kg i.p.) to mice significantly increased locomotor activity (total distance and number of rearing movements). The effect of p-hydroxycocaine was more active or comparable with that of cocaine, indicating that this metabolite is an active metabolite of cocaine.