Daily administration of cocaine (15 mg/kg i.p. x 3 days) led to a decrease in the total amount of 15 nM [3H]dopamine uptake in rat nucleus accumbens with no change in uptake in the striatum when tested 24 h after the last injection. There was an increase in the Km for dopamine uptake in the nucleus accumbens of cocaine-treated rats, with no change in the Vmax. Furthermore, cocaine was a more potent inhibitor of [3H]dopamine uptake in vitro in the nucleus accumbens of rats treated with cocaine than in those which had received saline.