Serum thyroglobulin (TG) is normally under TSH control. Serum TG levels are elevated during increased thyroid gland stimulation and suppressed by exogenous thyroid hormone. High serum TG levels are also found with thyroid gland damage and in patients with differentiated thyroid neoplasms. Congenital T4-binding globulin deficiency was found in this study to be an additional condition in which serum TG levels may be elevated. Elevated TG levels were found in 13 of 36 patients (36%) with congenital TBG deficiency compared to 1 of 27 unaffected relatives (4%). Mean TSH and free T4 index values were not significantly different. A postulated mechanism involves transient TSH stimulation of the thyroid after transient small declines in circulating free hormone levels due to the decreased extrathyroidal pool of thyroid hormone associated with T4-binding globulin deficiency.