Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation.