To examine the decline in risk of endometrial cancer after discontinuation of use of conjugated estrogens, we conducted a case-control study in a prepaid health plan. We identified 318 patients who had endometrial cancer but had no history of bilateral oophorectomy and had been in the Southern California (United States) Kaiser Foundation Health Plan for more than 10 years. For each patient, one or two control members were selected, 599 in all, matched for age and duration of membership at the time of cancer detection and who had had neither hysterectomy nor bilateral oophorectomy. A history of prescriptions for conjugated estrogens and of potential confounders was obtained for each subject by reviewing outpatient medical records. Rate ratios (RR) contrasting users with nonusers were estimated by time of latest prescription. We found that estrogen-induced risk of endometrial cancer decreases rapidly as the estrogen-free interval increases. The RR estimates, adjusted for duration of use and potential confounding factors, declined from 5.0 for those receiving their latest prescription within 24 months (95 percent confidence limits [CL] = 2.6-9.8), to 1.8 for those receiving their latest prescription within 24 to 48 months (CL = 0.9-3.7), to values near one for each latest prescription interval earlier than 48 months ago (P for trend = 0.00004). For those who used conjugated estrogens extensively (five or more prescriptions, five to 10 years ago), the RR estimate declined from 5.1 for those whose latest prescription was within two years to 0.6 yr for those whose latest prescription was four to five years previously (P for trend = 0.05).