Treatment with nafarelin, a gonadotropin-releasing hormone agonist, reversibly inhibits ovarian function and induces hypoestrogenemia. To determine the efficacy of such hormonal manipulation in the treatment of endometriosis, we randomly assigned 213 patients with laparoscopically confirmed endometriosis to receive, for six months, either nafarelin by nasal spray (400 or 800 micrograms per day) or oral danazol (800 mg per day). Placebo nasal spray and placebo tablets were used to double blind the study. Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society's scoring system. More than 80 percent of the patients in each treatment group had a reduction in the extent of disease as assessed by laparoscopy. The mean laparoscopic scores decreased from 21.9 to 12.6 with 800 micrograms of nafarelin, from 20.4 to 11.7 with 400 micrograms of nafarelin, and from 18.4 to 10.5 with danazol (P = 0.0001 within each group; there were no statistically significant differences between the groups). The percentage of women with severely painful symptoms of endometriosis decreased from about 40 percent to 5 to 10 percent, whereas the percentage with no or minimal discomfort rose from 25 to 70 percent. Of the 149 patients who tried to become pregnant, 58 (39 percent) succeeded after the completion of treatment; similar rates of pregnancy applied to the three treatment groups. Danazol use decreased high-density lipoprotein levels and increased low-density lipoprotein levels. These changes were not observed in nafarelin users, but a higher percentage of them reported hot flashes and decreased libido. We conclude that nafarelin is an effective agent for treating endometriosis and has few side effects other than hypoestrogenism.