Catechol-O-methyltransferase (COMT) plays a crucial role in the regulation of central dopaminergic systems. We examined the allelic association of a functional polymorphism of the COMT gene with the clinical manifestations and the response to antipsychotics of 100 schizophrenic patients and 201 healthy controls from the general Japanese population. No statistically significant difference was observed in the allele and genotype frequencies between the schizophrenic patients and the healthy controls. The daily neuroleptic dosage that patients received during their maintenance therapy was significantly higher in patients with the L/L genotype than in the other patients (P < 0.05). The present results suggest that the presence of the COMT genotype does not help in evaluating the susceptibility to the development of schizophrenia, but that it may help in the estimation of treatment-resistant features of schizophrenia. © 2003 Wiley-Liss, Inc.