BACKGROUND: Physiologic evidence suggests that use of alcohol increases the risk for breast cancer through a hormonal mechanism, but the relationship among breast cancer, alcohol, and postmenopausal hormones (PMH) remains unclear. OBJECTIVE: To examine the relation between concurrent use of alcohol and PMH and invasive breast cancer. DESIGN: Prospective cohort study SETTING: Nurses' Health Study. PARTICIPANTS: 44 187 postmenopausal women. MEASUREMENTS: Self-reported data on PMH use and breast cancer obtained from biennial questionnaires completed from 1980 to 1994 and average alcohol consumption in 1980, 1984, 1986, and 1990. RESULTS: 1722 women developed invasive breast cancer. Risk for breast cancer was elevated in women who currently used PMH for 5 or more years and did not drink alcohol (relative risk, 1.32 [95% CI, 1.05 to 1.66]) and those who never used PMH but drank 20 or more g (1.5 to 2 drinks) of alcohol daily (relative risk, 1.28 [CI, 0.97 to 1.69]). Current users of PMH for 5 or more years who consumed 20 or more g of alcohol daily had a relative risk for breast cancer nearly twice (1.99 [CI, 1.42 to 2.79]) that of nondrinking nonusers of PMH. A hypothetical postmenopausal woman whose lifetime risk for breast cancer is 4% could increase her risk to 8% with 5 or more years of current PMH use and consumption of more than one alcoholic drink daily. CONCLUSIONS: Both alcohol consumption and PMH use were associated with an increased incidence of breast cancer. Women who are currently taking PMH may want to consider the added risks of regular alcohol consumption.