Premenopausal women in affluent societies are protected from heart diseases which kill large numbers of men. The basis for this sex difference and the loss of protection with menopause is unknown. The hypothesis offered is that the greater incidence of heart diseases in men and postmenopausal women compared with the incidence in premenopausal women is due to higher levels of stored iron in these two groups. The hypothesis is supported by observations of (1) myocardial failure in iron strong disease, (2) accumulation of stored iron with age in men, and (3) accumulation of stored iron after menopause to levels found in men. In addition, the heart diseases of affluence are rare among impoverished peoples who are often iron deficient. The depletion of iron stores by regular phlebotomy could be the experimental system for testing this hypothesis, and a preventive therapy if the hypothesis is confirmed.