The behavioral "reverse tolerance" to d-amphetamine in rats has not been clearly established for the high-dose, sustained d-amphetamine exposure relevant to human behavioral toxicity, especially the amphetamine psychosis. We have looked for alterations in the d-amphetamine response following pretreatment by a newer pharmacologic intervention, the continuous chronic unilateral infusion of highdose d-amphetamine into the caudate-putamen. We found that the circling response to a subsequent intraperitoneal injections of d-amphetamine is consistently ipsilateral compared to saline controls, suggesting tolerance development. This finding, and that of minimal apomorphine-induced rotation in these animals, is discussed in terms of a functional imbalance of right and left nigrostriatal dopamine activity, possibly due to dopamine depletion.