We measured total body and regional (lumbar spine, femoral neck, Ward's triangle, and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically treated with suppressive doses of levothyroxine (L-T-4). Treatment was administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38 patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients were followed at our institution and treated with the minimal amount of L-T-4 necessary to suppress TSH. At the time of evaluation, free T-3 was normal in all cases, whereas free T-4 was increased in 17 (36.2%). The mean daily dose of L-T-4 was 154.3 +/- 5 mu g, and the mean duration of treatment was 10.1 yr. We found no significant difference between patients and age- and weight-matched controls in BMD at any site of measurement. BMD was not correlated with duration of therapy, cumulative or mean daily dose of L-T-4, serum levels of free T-4, free T-3, and osteocalcin. There was no difference between patients and controls in serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked telopeptide of type I collagen or in the concentrations of two markers of thyroid hormone action (sex hormone-binding globulin and amino-terminal propeptide of type III procollagen). Our data suggest that L-T-4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion has no significant effect on bone metabolism or bone mass.