A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients.