Ischemic cerebrovascular disease (ICVD) is a multifactorial disease caused by the interactions of several genetic and environmental factors. Tobacco smoke is a major cause of both cancer and vascular disease. Although its carcinogenic role via induction of DNA damage and mutation is well established, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in the intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNAis modulated by detoxification enzymes, including glutathione S-transferase (GST). We examined whether polymorphisms in this gene, as well as the angiotensin-converting enzyme (ACE) gene influence the risk of ICVD on smoking status. DNA was analyzed for deletions in the GST M1, T1, and ACE genes by polymerase chain reaction (PCR). No significant association was observed between GST null genotype and ICVD, even in smokers. However, a significant association between ACE and ICVD was observed only in smokers (chi(2) = 0.023, p < 0.05). We conclude that GST polymorphism is not a risk factor for the development of ICVD through smoking and suggest a high probability that ACE polymorphism may contribute to the odds of ICVD in smokers.