Abstract The purpose of this study was to assess: (1) the risk of breast cancer associated with use of ovulation-inducing agents (such as clomiphene citrate) as treatment for infertility; and (2) the risk associated with ovulatory abnormalities that result in infertility. We performed a case-cohort study among 3837 women evaluated for infertility at clinics in Seattle, Washington, at some time during 1974–1985. Computer linkage with a population-based tumor registry was used to identify women diagnosed with breast cancer before January 1, 1992. Data regarding infertility testing and treatment were abstracted from the infertility clinic medical records for women who developed breast cancer and a randomly selected subcohort. Twenty-seven women in the cohort developed in situor invasive breast cancer, in comparison with an expected number of 28.8 cases (standardized incidence ratio, 0.9; 95% confidence interval (CI), 0.6–1.4). Infertile women with evidence of an ovulatory abnormality were at a risk of breast cancer similar to that of women whose infertility was believed to be due to other causes. The risk among women who had taken clomiphene was reduced relative to infertile women who had not used this drug (adjusted relative risk, 0.5; 95% CI, 0.2–1.2), but the reduction in risk did not increase with duration of use. The possibility that use of clomiphene as treatment for infertility lowers the risk of breast cancer should be examined in other, larger studies.