OBJECTIVE To examine endocrine and clinical responses to long-term administration of RU486 in patients with endometriosis. METHODS Prospective open trial. METHODS Faculty practice of the authors. METHODS Six normally cycling women with endometriosis were recruited. METHODS Subjects received RU486 100 mg/d for 3 months. METHODS Hormonal changes during RU486 were compared with control data obtained in the preceding cycle during the early follicular phase. Clinical responses were determined by patient assessment and second-look laparoscopy. RESULTS All women became amenorrheic, and daily urinary levels of ovarian steroid metabolites remained acyclic. Mean luteinizing hormone (LH) (P less than 0.02) and LH pulse amplitude (P less than 0.05) were increased without changes in LH pulse frequency. An antiglucocorticoid effect was demonstrated by an increase in serum cortisol (P less than 0.01) and adrenocorticotropic hormone (P less than 0.05) levels. Treatment resulted in an improvement in pelvic pain in all subjects without significant change in the extent of disease as evaluated by follow-up laparoscopy. CONCLUSIONS Daily administration of RU486 results in acyclic ovarian function and improvement in the subjective painful symptoms of endometriosis.