Two patients with goitrous cretinism were studied by use of I-131 and chromatographic analyses of the thyroid gland, plasma and urine. These studies showed normal mechanisms existed to carry iodine through the steps of organic binding of iodide and deiodination of free iodotyrosines. There was nearly complete failure to form iodothyronine derivatives (e.g., thyroxine and tri-iodothyronine). The nature of this reaction in the normal thyroid is not known and the nature of a defect at this stage can only be the subject of speculation. The possible mechanisms involved are discussed in the light of current concepts of thyroidal metabolism of iodine.