The effect of long-term L-thyroxine (L-T4) therapy on axial skeleton bone density was studied in 31 premenopausal women; the bone densities of these women were compared with the bone densities of 31 age- and weight-matched women without thyroid or bone abnormalities. The women receiving L-T4 therapy had been receiving the medication for a minimum of five years. There was no difference in calcium intake or excretion between the L-T4—treated women and the controls. Women receiving L-T4 had increased serum thyroxine concentrations (134 ± 5 vs 95 ± 3 nmol/L [10.4 ± 0.4 vs 7.4 ± μg/dL]), an increased free thyroxine index (9.4 ±0.4 vs 6.8 ±0.2), and decreased serum thyroid-stimulating hormone concentrations (0.9±0.2 mU/L vs 2.1 ±0.3 mU/L [0.9±0.2 vs 2.1 ±0.3 μU/mL]). Serum thiodothyronine concentrations were normal and were similar in both groups. Women treated with L-T4 had a 12.8% lower bone density at the femoral neck and a 10.1% lower bone density at the femoral trochanter compared with matched controls. In contrast, lumbar spine bone density was similar in the two groups. The data suggest that long-term L-T4 therapy, which is often given at supraphysiologic dosages, may predispose patients to decreased bone density in the hip and may increase the risk of agerelated bone loss. It is advisable, therefore, to employ a dosage of L-T4 that is carefully monitored to avoid the long-term use of dosages that are excessive for the thyroid condition being treated.