To determine whether the long-acting injectable progestational contraceptive DMPA, depot-medroxyprogesterone acetate, alters the risk of breast cancer in women, a hospital-based case-control study was conducted in five participating hospitals in Nairobi, Kenya, Mexico City, Mexico, Bangkok, Thailand (two hospitals), and Chiang Mai, Thailand. 869 women with newly diagnosed breast cancer who were young enough to have used DMPA for contraception, and 11,890 women of similar age who had been admitted to hospital for conditions unrelated to steroid contraceptive use, were interviewed to obtain information about previous use of steroid contraceptives and suspected risk factors for breast cancer. DMPA had been used by 12.5% of cases and 12.2% of controls. Relative risk (95% Cl) in women who had ever used DMPA was 1.21 (0.96, 1.52). Risk was increased within the first 4 years of initial exposure, mainly in women under 35 years. This observation did not seem to result from selective surveillance for breast cancer in DMPA users. Risk did not increase with duration of use, and was not increased in women who had started to use DMPA more than 5 years previously. These results provide reassurance that women who have used DMPA for a long time and who initiated use many years previously are not at increased risk of breast cancer.