This is the first study of a possible molecular genetic basis for schizophrenia with obsessive-compulsive disorder (OCD). We performed a case-control association study of the catechol-O-methyltransferase (COMT) Val158Met polymorphism in schizophrenia-OCD patients, OCD and healthy controls. One hundred and thirteen schizophrenia-OCD patients, 79 OCD patients and 171 control subjects were genotyped for the Val(158)Met polymorphism in the COMT gene. There was no significant difference in allele and genotype distribution of the COMT gene between schizophrenia-OCD patients and healthy controls. The low-activity Met allele and Met/Met genotype were more frequent in OCD men than in schizophrenia-OCD and control individuals. This difference, however, was not statistically significant following correction for multiple comparisons. These results do not support the hypothesis that the COMT Val158Met gene polymorphism is associated with liability to schizophrenia-OCD.