We studied the association between estrogen replacement therapy (ERT) and the risk of breast cancer as part of the Cancer and Steroid Hormone Study. All subjects in the analysis were postmenopausal women enrolled from eight geographic areas. Women 25 to 54 years old with newly diagnosed breast cancer were identified through population-based tumor registries and diagnosed between Dec 1, 1980, and Dec 31, 1982. Controls were selected from the same eight geographic areas by the random digit dialing of residential telephone numbers. Analyses included 1369 cases and 1645 controls. Among women with bilateral oophorectomy, the relative risk of breast cancer for women who had ever used ERT was 1.3, compared with women who had never used ERT. Among women who had undergone hysterectomy but who still had at least one ovary, the relative risk was 1.1; among women who reported a natural menopause, the relative risk was 0.8. Overall, the risk of breast cancer did not appear to increase appreciably with increasing ERT duration or latency, even for durations and latencies of 20 years or longer.