To determine if differing degrees of levothyroxine (LT(4)) suppression therapy for benign and malignant thyroid disease are associated with proportionately increased rates of bone loss, this longitudinal assessment of bone densitometry changes (single-photon and dual-photon absorptiometry) was conducted in three groups of subjects: 24 thyroid cancer patients who were treated with near-total thyroidectomy, radioiodine ablation, and aggressive LT(4)-suppression; 44 patients who were treated with more conservative LT,suppression for benign thyroid disorders; and 24 normal controls. Bone densitometry values were adjusted for age, weight, height, and menopausal status. The rates of bone loss in benign LT(4)-suppressed patients were greater than those in controls at the midradius, distal radius, lumbar spine, and femoral neck. The rates of loss in the thyroid cancer patients were also greater than those in the controls at all four sites and greater than in the benign LT(4)-suppressed patients at the midradius, distal radius, and femoral neck but not in the lumbar spine. Rates of bone loss were not significantly correlated with LT(4) dose or with the serum level of T-4 or TSH. LT(4)-suppression therapy for benign thyroid disease is associated with accelerated bone loss. More aggressive LT(4)-suppression for thyroid cancer is associated with even greater bone loss, particularly in cortical bone regions. These risks must be weighed against the benefits of LT(4) therapy in individual patients.