Family-based studies have been conducted with restriction fragment length polymorphism (RFLP) analysis for testing association between polymorphisms for the catechol-O-methyltransferase (COMT) locus and schizophrenia in 49 Caucasian nuclear families consisting of fathers, mothers and offspring affected with schizophrenia. The present results did not support the hypothesis that the COMT gene might play an important role in predisposing an individual to a genetic risk for schizophrenia. Neither did we find a significant association of the COMT locus with violent behaviour in schizophrenia. Nevertheless, there may be a susceptibility gene for schizophrenia in a distinct region from the COMT locus on chromosome 22q, as a genome scan has suggested recently.