Although oxidative stress is a cardinal feature of bronchial asthma, the role of interactions between environmental oxidant/antioxidant exposures and antioxidant genes in asthma aetiology has yet to be determined. The present study was conducted to investigate whether two common polymorphisms -21A > T and -262C > T of catalase (CAT) gene are associated with susceptibility to asthma in a Russian population and to test the hypothesis that the asthma risk attributed to CAT genotypes could be dependent on both oxidant (tobacco smoking) and antioxidant (fruit and vegetable intake) exposures. A total of 429 unrelated Russian individuals from Central Russia were recruited in the study, including 215 asthmatics and 214 sex- and age-matched healthy controls. Genotyping analysis for the CAT gene polymorphisms was performed by PCR-RFLP assays. The frequencies of both allele -21A (OR 0.73 95%CI 0.55-0.96 p = 0.03) and -21AA CAT genotype (OR 0.42 95%CI 0.23-0.76 p = 0.004) were higher among asthmatics than among healthy controls. The frequency of -21AA genotype of the CAT gene was significantly higher in patients with allergic (OR 0.47 95%CI 0.25-0.92 p = 0.024) and nonallergic (OR 0.32 95%CI 0.14-0.71 p = 0.004) asthma in comparison with controls (at the Bonferroni corrected p value less than 0.025). Polymorphisms -21A > T and -262C > T of the catalase gene were in a positive linkage disequilibrium (p < 0.0001). Smokers who carried -21AA genotype had an increased risk of nonallergic asthma (p = 0.002), whereas nonsmoker carriers of this genotype did not have the risk of any variant of the disease. Notably, no association of CAT genotype -21AA with asthma was found in high fruit and vegetable consumers, whereas low fruit and vegetable consumers (one time per day or less often) possessing this genotype were at increased risk of both allergic (p = 0.013) and nonallergic (p = 0.008) asthma. This is the first study reporting an association of polymorphism -21A > T of the catalase gene with allergic and nonallergic asthma. We also found, for the first time, that cigarette smoking and fruit and vegetable intakes have potentially inverse modifying influences on the asthma risk in individuals with -21AA CAT genotype and that the gene-environment interactions that were found support the biologic plausibility of catalase gene for the development of bronchial asthma.