Five infants with congenital hypothyroidism were found to have persistently elevated levels of serum thyrotropin (TSH) for six to 24 months after administration of adequate doses of thyroxine. In these infants, the hypothalamic-pituitary threshold for TSH suppression by thyroxine seems to be unusually high. These observations suggest that serum TSH levels should not be the sole criterion for evaluating adequacy of thyroid hormone replacement during the initial months of therapy for congenital hypothyroidism.