A 35-yr-old goitrous cretin had a PBI of 9.3 μg/100 ml, a serum thyroxine (T4) by column of less than 1.0 μg/100 ml, a low resin triiodothyronine (T8) uptake and a plasma thyrotropin (TSH) of 65 ng/ml. Maximum thyroidal uptake was 73% at 24 hr and radioiodine was not discharged by perchlorate. The protein-bound radioactivity was not extractable with butanol and appeared in the initial effluent from a Dowex 1-X2 column. The thyroidal and serum iodoproteins were characterized by DEAE cellulose chromatography and Sephadex G-200 gel filtration, and by radioautography and direct counting of segments after agarose and Pevikon electrophoresis. Serum 127I and radioiodine were bound to albumin. Following “total” thyroidectomy, the PB127I and radioiodine both disappeared from the serum with rates similar to those of serum albumin. Incubated thyroid slices released only the iodoalbumins and iodide. Thirty per cent of thyroidal radioactivity was in the 105,000 ×g soluble fraction, half as iodoalbumin and half as thyroglobulin (TG). Salting-out curves, sucrose gradient ultracentrifugation and immunological studies suggested that TG was similar to normal TG. After hydrolysis, 71% of the radioactivity in TG was in monoiodotyrosine (MIT) and diiodotyrosine (DIT), and 12% T4 and T3. When further purified, crude iodoalbumin consisted of 60% iodoalbumin (TA) and 40% as iodoprealbumin (TPA). These proteins were further characterized by Ouchterlony gel diffusion and immunoelectrophoresis, thyroxine binding, and amino acid analysis. After hydrolysis 87% of the radioactivity in TA and TPA was in MIT and DIT and 3% in T4 and T3. These data suggest that the thyroid gland in this patient synthesized TG but could not hydrolyze and release its biologically active thyronines. Further, the gland could take up iodinate and release serum albumin and prealbumin.