The present study was undertaken to examine the effects of cyclic administration of low-dose progestogen on endometrial carcinogenesis in mice. A total of 115 female ICR mice, 10 weeks of age, were divided into four experimental and control groups. Mice in groups 1-3 received laparotomy and were injected with N-methyl-N-nitrosourea (MNU) solution at a dose of 1 mg/100 g body weight to the left uterine tube and with normal saline to the right uterine tube. From one week after the MNU exposure, groups 1 and 2 were given 5 ppm 17 beta-estradiol (E2)-containing diet throughout the experiment. Mice in group 1 received 5 s.c. injections of medroxyprogesterone acetate (MPA) (2 mg/mouse) at intervals of 4 weeks from week 7. Group 3 was treated with MNU/normal saline alone. Group 4 consisted of mice treated with MPA alone. At the termination of the experiment (week 30), all animals were killed and autopsied for pathological examinations. It was found that adenocarcinomas and preneoplastic lesions developed in the bilateral uterine corpora in mice of groups 1-3. MPA treatment significantly decreased the weight of the uterine corpus (P < 0.05) and the incidences of endometrial adenocarcinoma and atypical or adenomatous (P < 0.001) but not cystic glandular hyperplasias in the MNU/E2-treated groups. Additionally, MPA treatment tended to decrease the proliferating cell nuclear antigen-labeling index in endometrial glandular cells. These data indicate that MPA, even at low dose, has an inhibitory effect on mouse endometrial carcinogenesis induced by MNU and E2.