Animal studies have yielded conflicting results on the carcinogenicity of long-acting progestins. Since more than 1.5 million women worldwide are currently receiving injections of a contraceptive progestin, depot medroxyprogesterone acetate, this is potentially an important public health problem. We obtained information on the occurrence of breast, uterine, and ovarian cancer among 5,000 black women attending a metropolitan hospital's family planning clinic who had received injections of medroxyprogesterone for contraception (between 1967 and 1976). The women were followed up for four to 13 years after their initial medroxyprogesterone injection. We compared the observed number of cancer cases in these women with the expected number based on annual age-, race-, and sex-specific rates derived from National Cancer Institute data. During more than 40,000 woman-years of observation, we found no evidence of an increased risk of developing cancer of the breast, uterine corpus, or ovary in these women. After adjusting for possible underascertainment of cancer because of incomplete follow-up, we found the relative risk for medroxyprogesterone users to be 0.7 for breast cancer (95% confidence limits, 0.3 to 1.4), 1.2 (95% confidence limits, 0.1 to 6.7) for cancer of the uterine corpus, and 0.8 (95% confidence limits, 0.1 to 4.6) for ovarian cancer.