Glutathione S-transferase polymorphisms (GST) were examined in 142 cases with ischemic cerebrovascular disease (ICVD) to explore whether the GST polymorphisms confer a risk to an individual to develop ICVD. Tobacco smoke is a major cause of both cancer and vascular disease. The subjects were therefore stratified with ICVD for smoking status, and then the authors examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of ICVD. The GST genotype was analyzed by the polymerase chain reaction. Neither GSTM1 nor GSTT1 genotypes in the ICVD group was significantly different from the control group (n=344), even in smokers. The authors attempted the combined analysis for GSTM1 and GSTT1 genotypes in ICVD for smoking status. No significant association was observed among the combined genotypes and ICVD. The observations do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for ICVD, even in smokers. However, this approach provides a way of addressing the hypothesis that environmental genotoxins could play a role in the etiopathogenesis of ICVD.