An in vivo receptor binding technique was applied to evaluate the affinities of risperidone and haloperidol for dopamine-D2 receptors (D2) and serotonin-5-HT2 receptors (5-HT2) in rat brain with [3H]YM-09151-2 and [3H]ketanserin as selective ligands. Radioactivities were obtained in the striatum frontal cortex, and cerebellum of the rats treated with the ligands. Time course study of receptor occupancy at 25 to 250 min after single doses of the drugs (1 mg/kg, IP) showed higher 5-HT2 occupancy in the frontal cortex and lower D2 occupancy in the striatum by risperidone than by haloperidol. Dose-response analysis of receptor occupancy revealed risperidone demonstrated higher binding affinity for 5-HT2 than for D2, while the reverse was observed with haloperidol. It appeared that risperidone (1 mg/kg, IP), but not haloperidol (1 mg/kg, IP), demonstrated regional selectivity in D2 occupancy favouring frontal cortex more than the striatum. That risperidone displayed a higher ratio of 5-HT2 to D2 in occupancy than haloperidol is in agreement with the previous findings obtained in vitro.