Previous behavioral, biochemical, and electrophysiological studies have indicated that amperozide, a putative atypical antipsychotic drug with potent 5-HT2 receptor antagonist potency, preferentially affects mesocorticolimbic, as compared to mesostriatal dopamine neurons. The present experiment utilized in vivo microdialysis to compare the effects of amperozide on dopamine efflux in medial prefrontal cortex versus caudate-putamen in the freely moving rat. The results demonstrated that amperozide produced a greater elevation of cortical dopamine. These results were similar to those observed with clozapine but not haloperidol.