The effects of acute and chronic treatments with haloperidol or clozapine on the binding of [3H]spiperone to D2 and 5-HT2 receptors were examined in 6 discrete regions of the striatum, n. accumbens and frontal cortex using quantitative autoradiography. Acute treatment with haloperidol, 0.1-2.0 mg/kg, i.p., produced a dose-dependent reduction to 60% of control in the binding of [3H]spiperone to D2 receptors in the striatum and n. accumbens and no effect on the binding of [3H]spiperone to 5-HT2 receptors in the striatum, n. accumbens or frontal cortex. Acute treatment with clozapine, 10-40 mg/kg, i.p., produced a dose-dependent reduction in D2-specific binding in both the n. accumbens and the striatum and also significant reductions to 24% of control in the binding of [3H]spiperone to cortical 5-HT2 receptors. Chronic treatment with haloperidol, 1 mg/kg/day, i.p., significantly increased (40-65%) the maximal number of D2-specific [3H]spiperone binding sites in the n. accumbens and the dorsolateral and ventrolateral regions of the striatum, whereas small increases (20-29%) were seen in the ventromedial, dorsomedial, rostral and caudal regions of the striatum. Chronic treatment with clozapine, 20 mg/kg/day, i.p., did not change the maximal number of D2 receptors in the n. accumbens or any region of the striatum. Chronic treatments with clozapine produced a decrease in the maximal number of cortical 5-HT2 receptors to 55% of control whereas haloperidol had no effect. This study demonstrates regional differences in the up-regulation of striatal D2 receptors following chronic treatment with haloperidol and different effects of a typical and atypical neuroleptic on 5-HT2 receptors following acute and chronic treatments.