In 1976 Cortese, Schneider and Salvatore (Eur. J. Biochem. 68 (1976) 121-129) showed that the thyroid gland protects newly synthesized, iodine and hormone poor thyroglobulin from immediate degradation. Since then there has been substantial progress in understanding the mechanism by which this selectivity of degradation occurs. Thyroglobulin in the follicular lumen is internalized mainly by receptor-specific endocytosis. Recycling of immature, poorly iodinated thyroglobulin back to the follicular lumen is the pathway most likely responsible for selectivity. Since additional carbohydrate groups are added to the immature thyroglobulin, it appears that this recycling occurs via the Golgi compartment. The molecular signal for recycling most likely involves the complex carbohydrates and probably is exposed GlcNAc groups. A thyroid-specific GlcNAc receptor has been identified and cloned. Other Tg-binding sites have been identified in the thyroid, but their physiological role remains to be determined.