Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of colorectal adenomas with special reference to interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in a male Japanese population. Cigarette smoking was strongly associated with increased risk of colorectal adenomas. Overall, neither the CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A significant trend for increased risk of colorectal adenomas associated with smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing trends did not differ by MspI genotype. The positive association between smoking and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and current smokers, adenoma risk did not differ according to the combination of CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to modify the risk of colorectal adenomas associated with cigarette smoking.