Eight stumptailed macaques were injected daily with 5 or 20 micrograms D-Ser(But)6des Gly luteinizing hormone releasing hormone ethylamide (LHRH agonist) for approximately one year in order to prevent ovulation. On the last day of treatment (7 monkeys) or during the mid-luteal phase of the first cycle after treatment (1 monkey), a laparotomy was performed. Uterine size was slightly smaller (P less than 0.01) than in controls with normal cycles (n = 6). A full thickness wedge of anterior uterine wall was excised and examined histologically. Five of the agonist-treated monkeys had endometrium consistent with an atropic or resting proliferative pattern, but in 2 the appearance varied from early proliferative to marked secretory. All appeared entirely benign. The remaining animal studied in the luteal phase after stopping treatment exhibited a normal secretory endometrium. Ovaries from 2 of the LHRH agonist-treated animals were also studied histologically and found to consist of follicles at various stages of maturation. The occurrence of endometrial activity in 2 of the 8 LHRH agonist-treated monkeys stresses the need for careful endometrial assessment during clinical trials involving repeated administration of LHRH agonists in women.