Compliance to distinct combinations of hormone replacement therapy was assessed in 331 postmenopausal women treated for 1 to 5 years in the Menopause Unit of a third level referral Academic Hospital. Forty nine women (15%) had interrupted therapy, mainly during the first year, while 29 (9%) never had their prescriptions filled. Forty five women (14%) followed the treatment intermittently or only sporadically completed the treatment as prescribed. Four main factors were analyzed for their eventual influence on compliance: the inclusion of progestins in the prescription, the source of referral, the severity of menopause-induced symptomatology, and the route of estrogen administration. The source of referral divided women into three groups: patients referred from a doctor, those addressed from the gynecology ward of the hospital, and women who directly asked to be taken as patients in the unit. The intensity of clinical manifestations was assessed through the Kupperman index. Only two variables, the addition of progestins (P < 0.02), and the oral route of estrogen administration (P < 0.01) determined lower levels of compliance. The other two factors did not induce significant changes in the attitude of the patients towards hormone therapy.