Since the incidence of endometrial cancer among estrogen-treated women at Wilford Hall Air Force Medical Center was not increased as reported by others, a prospective study was begun in 1975. With this data base, the cases of breast and endometrial cancer in estrogen and oral contraceptive users were reviewed. The incidence of mammary malignancy in postmenopausal estrogen users (141.0:100,000) was lower than that of the untreated women, ie, nonhormone users (342.3:100,000) (P less than or equal to .01). The incidence of breast cancer in the estrogen-progestogen users (67.3:100,000) was significantly lower than that of the untreated women and than that expected from the Third National Cancer Survey (188.3:100,000) and the National Cancer Institute (NCI) data (229.2:100,000) (P less than or equal to .01). Oral contraceptives also decreased the risk of breast carcinoma, since the incidence in users (10.3:100,000) was significantly lower than expected in this age group according to both the Third National Cancer Survey (53.3:100,000) and the NCI data (57.3:100,000) (P less than or equal to .01). Unopposed estrogen replacement therapy increased the incidence of endometrial cancer to 410.8:100,000, but progestogen added to estrogen therapy significantly decreased this incidence to 68.1:100,000 (P less than or equal to .0001). The estrogen-progestogen users also had a significantly lower incidence of endometrial carcinoma than the untreated women (258.3:100,000) (P less than or equal to .005). Oral contraceptives, particularly the combination pill with estrogen and progestogen in each tablet, are protective against adenocarcinoma of the endometrium. The incidence of endometrial cancer apparently increased in premenopausal women during our study from 10.9:100,000 women in the first five years to 41.9:100,000 during the last two years as birth control pill use declined from 8,693 users in 1975 to 5,563 users during 1981, primarily in women over the age of 35.