The possible association between lung cancer and a polymorphism of the CYP1A1 gene specific to African-Americans was examined using peripheral blood DNA from 144 incident cases of lung cancer and 230 population controls with detailed data on smoking and other risk factors for the disease. The CYP1A1 variant allele was present in 15.2% of controls and 16.7% of cases. The smoking-adjusted odds ratio for the presence of the variant allele in relation to lung cancer risk overall was 1.3 (95% confidence interval, 0.7-2.4). According to histological type, the strongest association was observed for squamous cell carcinoma (odds ratio, 2.1), but this result was compatible with chance (95% confidence interval, 0.8-5.9). Adenocarcinoma was not materially associated with the presence of the variant allele (odds ratio, 1.3; 95% confidence interval, 0.5-3.2). No important associations were observed upon stratification by several risk factors for lung cancer, including smoking history, occupational exposures to asbestos and motor vehicle exhaust, or low intake of the micronutrient antioxidants beta-carotene, vitamin E, or vitamin C. These results do not confirm an earlier report that this CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans.