Risk of epithelial ovarian cancer (EOC) attendant to use of hormone replacement therapy (HRT) was evaluated in a population-based case-control study of newly diagnosed EOC cases (n=256) and randomly selected population controls (n=1122). Telephone interviews were conducted to obtain information on history of HRT and several other covariates. Multivariate adjusted odds ratio (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression. The OR for ever use of HRT was 1.39 (95% CI: 1.01-1.93) compared to never use. Long-term use (>10 years) increased risk (OR: 1.62, CI: 1.05-2.50) although the trend p-value for duration of use was of only borderline significance (p=0.08). The relationship was stronger in women without hysterectomy (OR: 1.66, 95% CI: 1.14-2.41) or tubal ligation (OR: 1.56, 95% CI: 1.08-2.26). In this study, use of HRT is associated with an increased risk of EOC.