BACKGROUND The effect of adding progestins to estrogen therapy on the risk of breast cancer in postmenopausal women is controversial. METHODS To quantify the relation between the use of hormones and the risk of breast cancer in postmenopausal women, we extended our follow-up of the participants in the Nurses' Health Study to 1992. The women were asked to complete questionnaires every two years to update information on their menopausal status, use of estrogen and progestin preparations, and any diagnosis of breast cancer. During 725,550 person-years of follow-up, we documented 1935 cases of newly diagnosed invasive breast cancer. RESULTS The risk of breast cancer was significantly increased among women who were currently using estrogen alone (relative risk, 1.32; 95 percent confidence interval, 1.14 to 1.54) or estrogen plus progestin (relative risk, 1.41; 95 percent confidence interval, 1.15 to 1.74), as compared with postmenopausal women who had never used hormones. Women currently taking hormones who had used such therapy for 5 to 9 years had an adjusted relative risk of breast cancer of 1.46 (95 percent confidence interval, 1.22 to 1.74), as did those currently using hormones who had done so for a total of 10 or more years (relative risk, 1.46; 95 percent confidence interval, 1.20 to 1.76). The increased risk of breast cancer associated with five or more years of postmenopausal hormone therapy was greater among older women (relative risk for women 60 to 64 years old, 1.71; 95 percent confidence interval, 1.34 to 2.18). The relative risk of death due to breast cancer was 1.45 (95 percent confidence interval, 1.01 to 2.09) among women who had taken estrogen for five or more years. CONCLUSIONS The addition of progestins to estrogen therapy does not reduce the risk of breast cancer among postmenopausal women. The substantial increase in the risk of breast cancer among older women who take hormones suggests that the trade-offs between risks and benefits should be carefully assessed.