The purpose of this study was to clarify the efficacy of estriol for estrogen replacement therapy in postmenopausal women with undefined symptoms and to evaluate endocrinological changes during therapy in relation to clinical outcome. Administration of 2 mg estriol in 168 postmenopausal patients was markedly effective in 22.6% of cases, effective in 45.2%, fairly effective in 14.3%, and ineffective in 17.9% of cases. The plasma concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after administration of estriol decreased significantly (p < 0.001), by 52.2% and 32.9%, respectively for markedly effective cases, and by 39.1% and 48.0% for effective cases. In contrast, the plasma estradiol concentration remained unchanged. On the other hand, decreases in FSH and LH concentration were 13.9% and 5.9% for the fairly effective and 8.2% and 1.9% for ineffective cases, demonstrating a significantly lower decrease in plasma FSH and LH levels than in the markedly effective and effective cases (p < 0.001). For cases showing side-effects, the plasma FSH and LH levels decreased by 52.0% and 64.3%, respectively, whereas the plasma estradiol level remained unchanged. In conclusion, the efficacy of estriol was significantly correlated to the degree of decrease in plasma FSH and LH levels in patients with undefined symptoms. In addition, efficacy appeared to be correlated to the incidence of side-effects. The degree of reduction of FSH (39.1-52.2%) and LH (48.0-64.3%) from the baseline may possibly be used as a guide to the therapeutic hormone levels during HRT. The present results suggest that plasma gonadotropin levels could be a useful indicator in the management of patients undergoing estrogen replacement therapy.