Medroxyprogesterone acetate was administered orally at the daily dose of 50 mg for four months to 21 symptomatic women with moderate to severe endometriosis, staged according to the American Fertility Society classification. The efficacy of the therapy was evaluated prospectively by the patients' symptomatology, monthly pelvic examinations, and by restaging the disease at second-look laparoscopy during the last week of treatment. The effects of therapy on the serum gonadotropin and ovarian steroid levels and on the endometrium and the implants of endometriosis were also evaluated. Improvement of symptoms, pelvic nodularity, and tenderness occurred in 80% of the patients. The mean stage score of disease by the American Fertility Society classification decreased from 18.2 +/- 2 before therapy to 5.9 +/- 1 after therapy (P less than .005). Amenorrhea, breakthrough bleeding, and persistent cyclic bleeding occurred in 75, 20, and 10% of the patients, respectively. Ovulation was inhibited in all patients, but serum hormone changes were statistically significant only for LH, which decreased from 9.5 +/- 4 to 5.2 +/- 2 IU/L (P less than .001), and estradiol (E2), which decreased from 80 +/- 30 to 46 +/- 26 pg/mL (P less than .02). Atrophic changes and pseudodecidualized reaction occurred in both the endometrium and the implants of endometriosis. In summary, oral medroxyprogesterone acetate is effective in relieving symptoms and objectively improving endometriosis. Besides inducing a pseudodecidualized reaction and atrophic changes in the endometrium and ectopic implants, medroxyprogesterone acetate also suppresses ovulation and the serum levels of both LH and E2.