1. The regional distribution and pharmacological property of binding sites for perospirone, an atypical neuroleptic, in rat brain were examined by an in vitro binding assay. 2. A high degree of [3H]perospirone binding was observed in the frontal cortex, caudate putamen, nucleus accumbens, olfactory tubercle, lateral septum, choroid plexus, hippocampus and entorhinal cortex. 3. In cortical membranes, the frontal cortex and nucleus accumbens, 1 nM [3H]perospirone bound predominantly to serotonin 5-HT2A receptors (about 40% of specific [3H]perospirone binding) rather than to dopamine D2 receptors. 4. About 60% of binding sites specifically labeled with 1 nM [3H]perospirone were D2 receptors and about 20% were 5-HT2A receptors in striatal membranes and the caudate putamen. 5. [3H]Perospirone interacted mainly with 5-HT1A receptors in hippocampal membranes and the lateral septum. 6. These results suggest that perospirone has a broad binding activity and that predominant occupancy of 5-HT2A receptors in mesocortical and mesolimbic structures might concern the atypical profile of perospirone as an antipsychotic drug.