The relationship between lung cancer risk and work in the cotton textile industry was investigated in a large population-based case-control study in urban Shanghai, where the industry is a major employer of men and women. Personal interviews obtained occupational, smoking, and other information from 1405 newly diagnosed lung cancer cases and 1495 controls. A significantly low risk of lung cancer was associated with cotton textile employment [odds ratio (OR) = 0.7,95% confidence interval (CI) = 0.6-0.9]. In men, the decreased risk was observed among both smokers (OR = 0.7, 95% CI = 0.5-1.1) and nonsmokers (OR = 0.3, 95% CI = 0.1-1.0). In women, the risk was also decreased regardless of smoking status (OR = 0.8, 95% CI = 0.4-1.6 among smokers; OR = 0.9, 95% CI = 0.6-1.2 among nonsmokers). In both sexes, the reductions in risk tended to be greater for lung cancer cell types other than adenocarcinoma. Low risks were found regardless of occupations within the cotton textile industry; the OR for workers in textile processing who potentially had greater dust exposure was 0.8 (95% CI = 0.6-1.2), whereas the OR for those in other industry jobs was 0.7 (95% CI = 0.4-1.0). There was little difference in risk according to self-reported exposure to textile dust, and no clear trend with duration of employment or dust exposure. Reasons for the reduced risk of lung cancer in cotton textile workers without a dose response are unclear, although several methodological explanations were considered. The findings, however, appear consistent with prior epidemiological studies and are interesting in light of speculation about tumor-inhibitory factors, such as bacterial endotoxins, that are found in dusts from cotton and other fiber crops.