Hyperthyroidism and thyroid hormone substitutive therapy with serum iT3 in the normal range of values are known to lead to increased bone remodeling and loss of bone mass. We looked for a relationship between serum iT3 and bone metabolic or bone mass parameters in 402 euthyroid women aged 44-60. In a group of 93 premenopausal women, a group of 309 postmenopausal women, and a group of 118 untreated postmenopausal women, serum iT3 was higher in the women classified as having "high" bone turnover according to both alkaline phosphatases and hydroxyprolinuria values. In postmenopausal women, serum iT3 corrected for thyroid binding globulin (TBG) (T3c) was higher in those receiving no estrogen replacement therapy. In a longitudinal study (n = 131), the rate of changes in lumbar bone mineral content was associated with changes in T3c. A less favorable bone mass evolution was associated with an increase in serum T3c, and inversely. Data suggest that the relationship of iT3/bone metabolism is direct and not merely the consequence of estrogen induced changes in both iT3 and bone metabolism. iT3 should be explored at the bone cellular level as a possible mediator in bone metabolic changes occurring in menopause and many other clinical situations.