Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.