Reports of opposing changes in platelet 3H-dopamine uptake in neuroleptic-free versus neuroleptic-treated schizophrenic subjects have suggested an effect of neuroleptic treatment on this measure. We examined platelet 3H-dopamine uptake in rats treated with haloperidol or clozapine to determine if such treatment did affect platelet 3H-dopamine uptake. Neuroleptic drug treatment reduced platelet 3H-dopamine uptake in a dose- and time-dependent manner. After up to 4 weeks of treatment, these effects were reversed by the discontinuation of neuroleptic drug treatment. These data suggest that the effect of neuroleptic treatment in studies of platelet 3H-dopamine uptake could account for the variable findings in schizophrenia.