The interaction of SCH 23390 with central serotonin 5-HT2 receptors was studied in vivo on [3H]spiperone binding and in vitro on [3H]ketanserin binding. SCH 23390 inhibited [3H]spiperone binding in rat frontal cortex with an ID50 of 1.5 mg/kg i.p., thus being equipotent to the two 5-HT2 antagonists cinanserin and methysergide. In vitro, SCH 23390 competed with [3H]ketanserin with an IC50 of 30 nM. These data indicate that SCH 23390 also binds with high affinity to 5-HT2 receptors in rat brain.