Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using chi(2) analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (P(corr) = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.