Risk factors for ovarian cancer may differ between pre- and postmenopausal women. The authors used data from a multiethnic, population-based, case-control study, conducted between 1993 and 1999 in Hawaii and Los Angeles, California, to examine whether menopause modified the effect of ovulation on ovarian cancer risk. A structured questionnaire was administered to 558 histologically confirmed epithelial ovarian cancer cases and 607 population controls. Lifetime ovulatory (log)years were significantly associated with an increased risk of ovarian cancer (odds ratio = 1.78, 95% confidence interval: 1.24, 2.57), particularly among premenopausal women (odds ratio = 2.49) but not among postmenopausal women (odds ratio = 0.88) (p(interaction) = 0.006). Factors that induced anovulation, including oral contraceptives, pregnancy, and breastfeeding, were associated with a reduced risk of ovarian cancer. Among anovulation factors, prolonged oral contraceptive pill use provided a greater protective effect against premenopausal ovarian cancer than against postmenopausal ovarian cancer (for > or =5.4 years of use vs. never use: odds ratio = 0.28, 95% confidence interval: 0.15, 0.52 vs. odds ratio = 0.58, 95% confidence interval: 0.31, 1.08, respectively), but the difference was not significant (p(interaction) = 0.20). Association of breastfeeding and pregnancy with ovarian cancer risk was also similar between pre- and postmenopausal women (respective p(interaction) = 0.72 and 0.43). The authors' data support the hypothesis that lifetime ovulation is involved in the pathogenesis of pre- but not postmenopausal ovarian cancer, while the protective effects of anovulation factors persist from pre- to postmenopausal women.