Biologic evidence suggests that high body iron stores could promote development of cancer. Because a previous study had shown an association between prescribed iron medication and lung cancer risk in men, we examined recent iron use as well as 2 additional indirect measures of body iron stores, anemia and the total iron-binding capacity (TIBC) of plasma, in relation to subsequent risk of cancer in a larger cohort of 174,507 persons. Women, but not men, who reported recent iron use had a lower risk of lung cancer than those who did not [RR = 0.60, 95% confidence limits (CL) 0.37, 0.97] after adjustment for age and cigarette smoking. Women who had used iron appeared to remain relatively iron-depleted. Risk for other cancers was slightly, but not significantly, lower in women who used iron. Anemia (hemoglobin less than 12 g) was also associated with lower risk of lung cancer in women (RR = 0.61, 95% CL 0.61, 0.98), but not in men. TIBC, which is inversely related to body iron stores, was inversely related to risk of lung cancer in women in a graded fashion (RR = 0.41, 95% CL 0.23, 0.73 comparing highest with lowest quartile). In men, a protective effect of higher TIBC against lung cancer was suggested, but did not reach statistical significance. These indirect measures of body iron stores appeared to reflect iron stores better in women than in men, probably because variability in iron stores is greater in women and iron deficiency more prevalent. A possible alternative explanation for our findings is incomplete adjustment for the confounding effects of cigarette smoking. This could apply to iron use and hemoglobin level which were related to smoking, but not to TIBC, which was not. These data, which indicate lower risk of cancer in iron-depleted women, lend epidemiologic support to the hypothesis that high iron stores may increase cancer risk, at least for lung cancer.