Hormone replacement therapy (HRT) is commonly prescribed to alleviate the climacteric symptoms of menopause. Recent findings from the Women's Health Initiative has raised questions about the routine use of HRT due to the increased observed incidence of cardiovascular disease and of breast and ovarian cancers in the treatment arm of the trial. In the general population, the association between HRT use and risk of ovarian cancer has not yet been resolved. This association has not been evaluated in BRCA1 or BRCA2 mutation carriers who face very high lifetime risks of both breast and ovarian cancers. We conducted a matched case-control study on 162 matched sets of women who carry a deleterious mutation in either the BRCA1 or BRCA2 gene. Women who had been diagnosed with ovarian cancer were matched to control subjects by mutation, year of birth, and age at menopause. Information on HRT use was derived from a questionnaire routinely administered to women who were found to be carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between HRT use and the risk of ovarian cancer, stratified by mutation status and type of HRT. Compared with those who had never used HRT, the odds ratio associated with ever use of HRT was 0.93 (95% CI = 0.56-1.56). There was no significant relationship with increasing duration of HRT use. There was a suggestion that progestin-based HRT regimens might protect against ovarian cancer (odds ratio = 0.57) but this association was not statistically significant (P = 0.20). HRT use does not appear to adversely influence the risk of ovarian cancer in BRCA mutation carriers.