The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.