To examine the role of serotonin2 (5-hydroxytryptamine2, 5-HT2) receptors in schizophrenia, we determined the binding indices of 5-HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the radioligand in platelets obtained from 40 normal control subjects and 42 drug-free schizophrenic patients. We also examined the effect of neuroleptic drug treatment on the binding parameters (Bmax and Kd) of 5-HT2 receptors in platelets of schizophrenic patients. We observed that the Bmax of 125I-LSD binding in platelets of schizophrenic patients was significantly higher than in platelets of normal subjects. There was no significant difference, however, between the Kd of 125I-LSD binding in platelets of schizophrenic patients and normal control subjects. Furthermore, we found no correlation between Brief Psychiatric Rating Scale scores and either Bmax or Kd of 125I-LSD binding at the end of the drug washout period. We also observed that neither treatment with haloperidol nor treatment with thiothixine caused significant changes in Bmax and Kd of 125I-LSD binding in platelets of schizophrenic patients. However, both fluphenazine and trifluoperazine did significantly increase the Bmax of 125I-LSD binding without any significant change in the Kd values in platelets of schizophrenic patients. Our results thus suggest that platelet 5-HT2 receptors are increased in schizophrenia and that chronic treatment with fluphenazine and trifluoperazine, but not haloperidol or thiothixine, further increases the 5-HT2 receptor binding sites in platelets of schizophrenic patients.