The effect of cigarette smoking on the risk of early-stage endometrial cancer was evaluated in a population-based case-control study of women aged 40 to 69 years from upstate New York. Two hundred women with early-stage endometrial cancer diagnosed between 1979 and 1981, and 200 matched community controls were interviewed in person and asked about smoking habits and other risk factors. Statistical analysis revealed a significant decline in relative risk with increased smoking (P less than 0.05). This effect strongly modified the well-known increase in risk with body weight. Among smokers risk did not increase with body weight, whereas among nonsmokers risk increased rapidly with body weight, especially among nonsmokers in whom the peripheral conversion of androgens was the primary source of serum estrogen. Despite this apparent reduced risk for endometrial cancer, smoking remains a major health hazard for women as well as men.