Thirty-four perimenopausal women with uterine leiomyomas were treated with intramuscular injections of leuprolide acetate depot each 28 days for 6 cycles, and 12 of them after 168 days of no medication underwent a second 6-month therapy cycle. At the end of the observation period the expected improvement during treatment was maintained at cessation of therapy in 15 patients, due to the effect of the natural postmenopausal estrogen deficiency. Only 3 women underwent hysterectomy, due to the regrowth to baseline values of uterine size. It is concluded that the therapy with gonadotropin-releasing hormone analogs in perimenopause offers an effective alternative to surgery in the treatment of uterine leiomyomas.