Total body and regional bone mineral density (BMD) levels were determined in 26 premenopausal women with Hashimoto's thyroiditis receiving long-term physiological doses of levothyroxine sodium replacement therapy. The BMD levels of each patient were compared with the mean of the BMD levels of age-matched normal controls. The mean levothyroxine sodium dose was 111 +/- 6 micrograms/d, and the mean duration of treatment was 7.5 +/- 5.3 years (range, 1 to 24 years). Dietary calcium intake was similar in both groups, as were serum thyroxine, triiodothyronine, free thyroxine index, and thyrotropin levels. Women receiving the levothyroxine treatment had normal total body BMD levels but had significantly lower BMD levels at the femoral neck (-5.7%), femoral trochanter (-7.0%), Ward's triangle (-10.6%), both arms (right, -7.8%; left, -8.9%), and pelvis (-4.9%). In contrast, lumbar spine BMD levels were similar in the two groups. There was no correlation between the total body or different regional BMD levels and the duration or dosage of levothyroxine treatment or thyroid function test results. However, the z score of the femoral neck of these patients showed a significant negative correlation with their serum free thyroxine index levels. We conclude that patients receiving physiological doses of levothyroxine may have decreased bone density. Thyroid functions in patients receiving long-term levothyroxine treatment should be closely monitored and bone densitometry should be performed in patients at risk for osteoporosis.