Experimental and clinical studies suggest that oxidative stress is an important pathogenetic mechanism of both essential hypertension (EH) and cerebral stroke (CS). In this paper, we investigated, for the first time, the relationship between polymorphisms of two genes for antioxidant defense enzymes such as catalase (CAT) and flavin-containing monooxygenase 3 (FMO3) and the risk of CS in hypertensive patients. DNA samples obtained from 667 unrelated Russian patients with EH (306 patients with CS, and 361 patients without cerebrovascular accidents) were genotyped for polymorphisms -21A>T (rs7943316) of the CAT gene and E158K (rs2266782) of the FMO3 gene. We found that the -21AA CAT genotype is associated with increased risk of CS in hypertensive males (OR=1,77 95% CI 1,01-3,07). No significant differences in allele and genotype frequencies of the FMO3 E158K polymorphism have been revealed between the groups. The association analysis stratified by the environmental risk factors showed that the -21AA CAT genotype increased the risk of CS in male smokers (OR=2,33 95% CI 1,40-5,40) as well as in male alcohol abusers (OR=4,29 95% CI 1,22-15,12). In contrast, the variant genotypes such as an -21AT and -21TT of the CAT gene had a protective effect on the risk of CS in EH males with high or moderate physical activity (OR=0,30 95% CI 0,11-0,83) and in those men who did not have life stresses (OR= 0,51 95% CI 0,28-0,90). The protective effect of the variant genotypes was also observed in high fruit and vegetable consumers (OR=0,40 95% CI 0,17-0,93). This study is the first to show that the polymorphism -21A>T CAT is associated with increased risk of cerebral stroke in hypertensive men, however, the relationship between the polymorphism and risk of cerebrovascular disease depends on whether the patients have environmental risk factors or not.