To examine the association between ovarian cancer and prior hysterectomy or tubal ligation in light of various interpretations, we combined data from two previously conducted case-control studies of ovarian cancer. This included 450 women with histologically verified epithelial ovarian cancer and 454 age-matched women from the general population for whom data on prior pelvic surgery were available to estimate exposure odds ratios. Overall there was a nonsignificant deficit of case patients who had had a hysterectomy or tubal ligation (odds ratio (OR) = 0.9; 95% confidence interval (CI), 0.6 to 1.3). A protective effect of prior hysterectomy or tubal ligation was more apparent among women who had the surgery 20 or more years previously (OR = 0.6; 95% Ci, 0.3 to 1.1), women who had not used talc in their hygiene (OR = 0.6; 95% CI, 0.4 to 1.0), and women with mucinous tumors of the ovary (OR = 0.3; 95% CI, 0.1 to 1.0). Although these data do not clearly establish the validity of or mechanisms for an association between prior pelvic surgery and ovarian cancer, we speculate that such an association exists and may be mediated through absent or reduced uterine growth factors that reach the ovaries through the uteroovarian circulation, with mucinous tumors most dependent on such factors.