Data from two population-based case-control studies in the greater metropolitan Boston, MA (USA) were used to assess the association of self-reported use of antidepressants or benzodiazepine tranquilizers and epithelial ovarian cancer. Cases were women between 18 and 80 years of age diagnosed with epithelial ovarian cancer during two time periods: November 1978 through September 1981, and July 1984 through September 1987. Female controls were identified from Massachusetts town books and were frequency-matched to cases by age, race, and precinct of residence. In-person interviews assessed reproductive and medical histories as well as prescription medication use. Prior use of antidepressants or benzodiazepine tranquilizers exceeding one to six months was associated with an increased risk of ovarian cancer (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 0.9-4.8, and adjusted OR = 1.8, CI = 1.0-3.1, respectively). The association was confined primarily to women whose first use occurred before age 50 years (adjusted OR = 3.5, CI = 1.3-9.2, and adjusted OR = 2.7, CI = 1.3-5.6, respectively). No association was observed with respect to other non-hormonal medications reported.