Endometrial biopsies were obtained from postmenopausal women receiving 0.625 mg Premarin daily and either 2.5 or 5 mg norethindrone daily or 150 or 500 microgram dl-norgestrel daily for 10 days each month. Sample were taken during the estrogen-only phase of treatment and on the sixth day of combined estrogen/progestin administration. Progestin exposure caused marked morphologic and biochemical changes as well as features comparable with the premenopausal luteal phase. Thus, progestins oppose the stimulation of premarin to the postmenopausal endometrium. However, the currently recommended dosage of norethindrone and dl-norgestrel greatly exceed those necessary to suppress endometrial proliferation effectively. The recommended daily dosage may be lowered without losing protective effect. This reduction will probably minimize the risk of dose-dependent progestin side effects.