Since oral contraceptives have been used by more than 40 million American women, an association between oral contraceptives and ovarian cancer could have a substantial public health impact. The Centers for Disease Control, Atlanta, is studying this relationship as part of a multicenter, case-control study--the Cancer and Steroid Hormone Study. During the first ten months of the study, we enrolled 179 women aged 20 to 54 years who had been ascertained to have newly diagnosed ovarian cancer by eight population-based cancer registries. From the general population of those eight areas, we selected as controls 1,642 women with intact ovaries. Users of oral contraceptives had an age-adjusted risk of ovarian cancer developing of 0.6 relative to those who had never used them (95% confidence interval, 0.4 to 0.9). The risk of ovarian cancer decreased with increasing duration of oral contraceptive use and remained low long after cessation of use. These results were not accounted for by parity, infertility, or other potentially confounding factors. We estimate that more than 1,700 cases of ovarian cancer are averted each year by past and current oral contraceptive use among women in the United States.