This is a report of results from a case-control study of the relationship of the long-acting progestational contraceptive, depot-medroxyprogesterone acetate (DMPA) to risk of endometrial carcinoma. Prior use of DMPA and information on known and suspected risk factors for endometrial cancer were ascertained in personal interviews with 122 women with histologically confirmed disease and 939 controls selected from 2 hospitals in Bangkok and 1 in Chiang Mai, Thailand. Based on 3 exposed cases and 84 exposed controls, the relative risk of endometrial cancer was estimated to be 0.21 (95% confidence interval = 0.06, 0.79) in women who had ever used DMPA (but who had not first used DMPA in the year prior to diagnosis). All 3 exposed cases had also received estrogens pre-menopausally. Exposure to such estrogens enhanced risk of endometrial cancer and reduced the apparent protective effect of DMPA. Although based on small numbers of exposed women, the protective effect of DMPA appeared to last for at least 8 years after cessation of use. The reduction in risk of endometrial cancer is at least as great for DMPA as for combined oral contraceptives.