The authors report eight preterm infants with hypothyroxinemia who developed clinical features similar to those described in congenital hypothyroidism: prolonged jaundice, hypoactivity, lethargy, constipation, edema, and hoarse cry. All had low serum thyroxine, normal thyroid stimulating hormone, and normal thyroid binding globulin levels. After exclusion of other causes for the symptoms, thyroid replacement therapy was started, resulting in rapid resolution of symptoms and return to euthyroid status. Follow-up of these infants after cessation of therapy revealed normal growth and development and normal thyroid function. The authors therefore recommend a prospective study to investigate the incidence of hypothyroxinemia, frequency of associated clinical features, and the benefits of thyroid replacement therapy based on a randomized controlled trial.