The objective was to assess the significance of the catechol-o-methyltransferase (COMT) enzyme polymorphism in migraine. For this reason, 62 migraineurs and 64 healthy volunteers were included in the study. The analysis of COMT polymorphism was performed using PCR. The H/H genotype was more frequent in the control group than in the patients group (P50.032). The homozygous or heterozygous L allele was over represented in the migraineurs compared with the controls (P50.013). The L/L genotype was over represented in the migraineurs who also had a family history of migraine (P50.003). There was no relationship between aura and COMT genotypes. In conclusion, the COMT polymorphism may be of potential pharmacological importance regarding the individual differences in the metabolism of catechol drugs in migraineurs. Although altered catechoamine activity due to polymorphism of COMT gene may be one of the mechanisms involved in the pathogenesis of migraine, these mechanisms are not related to presence or absence of aura.