We examined the incidence of endometrial cancer in a large prepaid group practice in the Seattle area. From July, 1975, to July, 1977, there was a sharp downward trend in the incidence of endometrial cancer that paralleled a substantial reduction in prescriptions for replacement estrogens. Incidence rates were estimated for estrogen users and nonusers among women 50 to 64 years of age with intact uteri; current long-term users had an annual risk for endometrial cancer between 1 and 3 per cent, whereas nonusers had a risk less than 1/10th as great. These incidence rates remained fairly constant over time among users and nonusers; the drop in overall incidence soon after estrogen use declined suggests that the increased risk associated with estrogens falls quickly after discontinuation. The reduction in incidence of endometrial cancer in this group practice was part of a general decline in the United States after 1975. (N Engl J Med 300:218–222, 1979) THE first case–control studies that demonstrated a strong association between replacement estrogens and endometrial cancer were published in December, 1975.1,2 Further data supporting the association appeared in June, 1976.3 Despite these and subsequent publications,4,5 some doubt about the presence of a causal association remains.6,7 In addition, details of absolute risk in relation to dose, duration and other relevant factors have not been well defined. In this paper, we report on the experience of Group Health Cooperative of Puget Sound, a comprehensive health-care organization, in relation to endometrial cancer and replacement estrogen use. This study was part of an ongoing Group. © 1979, Massachusetts Medical Society. All rights reserved.