Normal and congenitally goitrous thyroid tissue was examined to identify the defective mechanism in the goitrous glands. 2. The uptake of [(131)I]iodide from the blood stream into the goitrous glands (average 74.9%) was significantly greater than normal (average 43.5%; P < 0.005), as was the rate of [(131)I]iodide release (goitrous t((1/2)) average 72.3hr., normal t((1/2)) average 198.7hr.; P0.025). 3. The l-[(131)I]-iodotyrosine-deiodinase activity was significantly (P0.02) greater than normal in goitrous-thyroid slices. 4. The 0.9%-sodium chloride-soluble proteins of [(131)I]-iodide-labelled thyroid glands were fractionated with ammonium sulphate: 68.7+/-4.0% of the total radioactivity appeared in the 35-45%-saturation precipitate from normal gland extracts, but less than 20% of the total radioactivity was in in this fraction from goitre extracts. 5. Ultracentrifugal analysis of 0.9%-sodium chloride-soluble proteins of goitrous glands showed no protein of S(20,w) 19-20s (thyroglobulin) even when the animals had previously received 0.1-2.0mg. of l-thyroxine/day intramuscularly for 40 days. The major proteins of goitrous glands had S(20,w) 3.2-7.6s. 6. The incorporation in incubated slices of [(14)C]proline and [(14)C]leucine into soluble proteins precipitated by 35-42%-saturated ammonium sulphate was markedly lower in goitrous tissue. 7. It was concluded that the goitrous tissue exhibited defective biosynthesis of thyroglobulin.
