Tail-tip plasma samples of intact and gonadectomized male and female Wistar rats were analyzed for cocaine and benzoylecgonine. The samples were obtained from immobilized subjects 10 and 30 min following the 1st and 22nd intraperitoneal injections of 10 mg/kg cocaine hydrochloride. Gender differences in plasma cocaine or benzoylecgonine levels were not observed after the first injection of cocaine because many of the samples were below the detection limit. Cocaine plasma levels were much higher after the 22nd injection, but gender differences were not observed either 10 or 30 min following cocaine administration. Plasma levels of benzoylecgonine were higher 30 min than 10 min after cocaine administration in intact and castrated male rats and ovariectomized female rats but not in intact female rats. These data show that, in rats, gender differences in cocaine metabolism may be observed after repeated cocaine administration, but the exact mechanism remains to be elucidated.