Biochemical parameters reflecting bone resorption [urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OH/Cr)] were related to serum estrogens [estrone (E1) and estradiol (E2)] in 262 healthy women including 158 patients receiving estrogen replacement therapy (ERT) for at least 6 months, 49 eugonadal women, and 55 untreated postmenopausal women. A significant (P < 0.001) correlation exists between serum E2 and Ca/Cr: Ca/Cr (mg/dl) = -0.00044 E2 (pg/ml) + 0.129 (n = 262; r = -0.37), serum E2 and OH/Cr: (OH/Cr (mg/g) = -0.049 E2 (pg/ml) + 18.76 (n = 262; r = -0.36), serum E1 and Ca/Cr: Ca/Cr (mg/dl) = -0.0003 E1 (pg/ml) + 0.127 (n = 261; r = -0.28) but not between serum E1 and OH/Cr. Women with circulating levels of E2 between 60 and 90 pg/ml have a significant (P < 0.01) reduction of Ca/Cr and OH/Cr when compared with those with lower levels of E2. Higher values of E2 do not provide additional benefit. We conclude that in postmenopausal women receiving an estrogen replacement therapy (ERT), a significant reduction of bone resorption is achieved when circulating levels of estradiol reach a value (60 pg/ml) corresponding to the one measured, in eugonadal women, during the last days of the early follicular phase of the menstrual cycle. We suggest that oral or percutaneous ERT should induce a minimal value of 60 pg/ml to prevent postmenopausal bone loss.