We determined the affinity of several typical and atypical antipsychotics for the 5-HT1C and 5-HT2 sites using radioligand binding assays. Most of the antipsychotics tested appeared to bind to 5-HT2 sites with affinities that were fairly high (i.e. pKi values between 7 and 9) and significantly higher than for 5-HT1C sites. In contrast, clozapine was found to have a significantly higher affinity for 5-HT1C than for 5-HT2 sites. Clozapine had the highest affinity for 5-HT1C sites of all the compounds tested. These findings are consistent with the hypothesis that an interaction with 5-HT2 receptors may be relevant to the clinical activity of typical antipsychotics. The findings also suggest, however, that an interaction with 5-HT1C sites may be relevant to the mechanism of clinical action of clozapine and, perhaps, of other atypical antipsychotics.