A woman in her 24th week of gestation was referred for treatment of hypothyroidism, after she underwent radioablation of the thyroid during the 13th week of gestation. Because of the high risk of hypothyroidism in the fetus, prenatal administration of intramuscular T4 to the fetus was begun at 32 weeks. The last dose of T4 was given 2 weeks before delivery; cord blood levels of T4 and T3 were undetectable and the TSH concentration was markedly elevated. The case illustrates several important physiological concepts regarding thyroid hormone and TSH metabolism in the fetalplacental unit, including the minimal placental permeability to iodothyronines and TSH, independent function (including feedback control) of the fetal hypothalamic-pituitary-thyroid axis, and the TSH response at parturition. In addition we suggest that administration of T4 to the hypothyroid fetus in utero is an acceptable modality of treatment and may help to minimize irreversible mental retardation in known high risk infants. However, further studies are necessary to assess the effectiveness and safety of this approach.