Tamoxifen, a synthetic antiestrogen, has been shown to be effective in reducing mortality from breast cancer and the occurrence of contralateral breast cancer. Tamoxifen is now being studied as a preventive of breast cancer among healthy women considered to be at high risk; preventive trials are now under way both in the USA and in Europe. We undertook a case-control study in Lyon and Dijon, France, to assess the effect of tamoxifen and other treatments for breast cancer on subsequent endometrial cancer. Through the use of clinicians' surveys in Lyon and a population-based cancer registry in Dijon, we identified 43 cases of endometrial cancer diagnosed at least 1 year after the diagnosis of breast cancer. We matched 177 controls to the cases for age, region, year of diagnosis of breast cancer, and survival from breast cancer. Tamoxifen had been used in 67% of cases and 60% of controls [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 0.60-3.5]. Relative risk of endometrial cancer increased with duration of tamoxifen use: less than 2 years, 1.5; 95% CI = 0.44-4.9; 2-5 years, 1.5; 95% CI = 0.42-5.6; more than 5 years, 3.5; 95% CI = 0.94-12.7. Radiotherapeutic castration increased the risk for endometrial cancer more than tamoxifen (OR = 7.7; 95% CI = 1.8-32.8).