Several lines of evidence suggest that psychosis is associated with altered dopaminergic neurotransmission. Dopamine is catabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT). We hypothesized that the genes encoding MAOA and COMT might contain genetic variation conferring increased risk to schizophrenia. In order to test this hypothesis, we genotyped the 941T > G and the promoter VNTR polymorphisms in the MAOA gene and the V158M COMT polymorphism in 346 DSMIV schizophrenics and 334 controls. We also genotyped the-287A > G COMT promoter polymorphism in 177 schizophrenics and 173 controls. No significant differences were found in allele or genotype frequencies between affecteds and controls for any of the polymorphisms. As both genes are involved in degrading catecholamines, we also sought evidence for additive and epistatic effects but none was observed. Our data, therefore, do not support the hypothesis that genetic variation in MAOA and COMT is involved individually or in combination in the etiology of schizophrenia.