Thyroglobulin (19 S, 660,000) (Tgb), the specific glycoprotein of the thyroid is the support of thyroid hormone biosynthesis. It is a dimer formed of 2 identical subunits (12 S, 330,000) containing a peptide chain of Mr 300,000 to which are associated through the asparagine of Asn-X-Thr (Ser) sequences, 2 types of carbohydrate units. The peptide chain is encoded in a 33 S mRNA of 8500 bases. The nature and number of Tgb genes, their transcription and the nuclear processing of premessenger RNA are unknown. However, the recent obtaining of clones of DNA complementary to Tgb mRNA will allow a rapid study of these structures and events. Tgb chains are synthesized on heavy polysomes associated with membranes of the endoplasmic reticulum. Nascent chains are then glycosylated by association of an oligosaccharide chain (GIcNAc)2 (Man)n (Glc)n' preassembled on a lipid carrier in the membrane, followed by removal of outer glucose and elongation in the Golgi membranes to produce branches of the type NeuNAc leads to Gal leads to GlcNAc. Possible roles for oligosaccharides in the structure and biosynthesis of Tgb are actively investigated. Then the fully glycosylated protein undergoes iodination that leads with a high yield to thyroid hormone formation according to a complex process critically depending upon the native 3-dimensional structure of the protein. Thyrotropin is likely to regulate Tgb production at the nuclear and cytoplasmic levels. Cell model systems for the study of Tgb biosynthesis and thyroid function are discussed.