OBJECTIVE To examine the effects of concomitant use of goserelin and medroxyprogesterone acetate (MPA) in the treatment of endometriosis. METHODS Thirty-eight women with laparoscopically confirmed endometriosis were treated with once-a-month s.c. injections of goserelin acetate 3.6 mg (Zoladex depot; Zeneca Pharmaceutics, Cheshire, United Kingdom) randomly combined with either MPA (100 mg daily; n = 19) or a placebo (one tablet daily; n = 19) in a double-blind trial. Symptoms and side effects were monitored for a treatment period of 6 months and a follow-up period of 6 months. Blood and urine samples were collected for the assessment of endocrine and biochemical parameters. A second-look laparoscopy was performed 6 months after the treatment in 29 women. RESULTS The extent of endometriosis was diminished similarly in both treatment groups, as were pelvic symptoms. Fewer women in the MPA group had hot flushes and sweating at 3 and 6 months of treatment. Sex hormone-binding globulin decreased in the MPA group but not in the placebo group. Consequently, the E2 index (E2/SHBG X 100), reflecting the free fraction of E2, fell more in the placebo group than it did in the MPA group. The increased urinary excretion of calcium observed during placebo treatment was prevented by MPA. CONCLUSIONS High-dose MPA combined with a GnRH agonist (GnRH-A) diminished some antiestrogenic effects of the agonist. A reduction in hypoestrogenic side effects and a possible bone-sparing effect can be regarded as beneficial, especially as the good effect of the GnRH-a on endometriotic implants and pelvic symptoms prevailed.