A number of patients with severe vasomotor symptoms of menopause, specifically hot flashes, are unable to take exogenous estrogens because of intolerance or contraindications. Others achieve less than satisfactory relief of symptoms with estrogen. A double-blind study was established to determine whether depomedroxyprogesterone acetate (DMPA) injeclable (Depo- Provera, Upjohn) could be used as a satisfactory substitute in these patients. The basis of the study was to evaluate clinical impressions that some menopausal patients taking DMPA for other purposes achieved relief from these distressing symptoms. Fifty-seven patients were treated with DMPA, 150 mg IM monthly, and 12 controls were given 1.5 ml sterile saline IM monthly. Serum FSH and LH were measured initially and serially. Clinical response was determined by the patients' estimates of the frequency and severity of their hot flashes. Of 57 patients in the treatment group, 51 (89.5%) were relieved of symptoms compared to 3 of 12 (25%) in the control group. DMPA can be an effective alternate to estrogen therapy in selected menopausal patients.