THIS LECTURE concerns the structure of thyroid stimulating hormone (TSH) and the relationships that have been found between TSH, luteinizing hormone (LH, ICSH) and human chorionic gonadotropin (HCG). Determination of the structures of TSH and LH has required years of purification and chemical studies in many laboratories including our own, but in just the past two years these efforts have resulted in a major increase in our knowledge of the glycoprotein hormones, that is, those polypeptide hormones which contain covalently bound carbohydrate as integral parts of their structures. Particularly important contributions have been made by Condliffe and Bates in the purification of TSH (1) and by Li, Papkoff and their colleagues (2,3) and by Ward and his colleagues (4,5,6) in their structural studies on LH. The major glycoprotein hormones of the pituitary and placenta are listed in Table 1 together with some of their chemical properties as these were known just 2 or 3 years ago. It is obvious that uncertainties and conflicting data existed at this time particularly for HCG and follicle stimulating hormone (FSH) but certain points, which bear emphasis, were very clear. First, obviously the carbohydrate of each hormone is covalently bound to the peptide portion; in the case of TSH and LH, the sugars constitute about 15% of the molecule while in HCG about twice as much was found. In TSH and LH the sugars are mannose, fucose, galactose, glucosamine, and galactosamine. The amino sugars are presumably N-acetylated. In bovine and ovine TSH and LH, little or no sialic acid is found; some is found in the human hormones. The biological significance of this charged molecule in human TSH and LH is uncertain although it is well established that in HCG (and FSH) the presence of sialic acid at the termini of oligosaccharide chains has a marked effect on hormonal activity (e.g., 8). Second, all have relatively large numbers of disulfide bonds in their structure. Third, all have been difficult to purify for a variety of reasons; for example, pituitary TSH and FSH are obtainable only in low yields. Thus from 100 lbs of bovine anterior lobes (20,000 lobes) we obtain 100-200 mg of fully purified TSH.