Glycoproteins constitute the most common class of viral and protozoal envelope proteins, mammalian serum proteins, plasma membrane receptors, transporters and ion channels. Although it has been suggested that such proteins may have heterogeneity of carbohydrate structures, the specific chemical nature and significance of such heterogeneity is not known. Using newly developed methods of lectin analysis of glycopeptides as well as high performance liquid chromatography (HPLC) analysis of enzyme-released sugars, we have elucidated at least 9 different carbohydrate variants of secreted TSH. Moreover, for the first time in any glycoprotein system we have elucidated major developmental and endocrine regulation of such glycosylation, and are currently studying the functional correlates of such regulated heterogeneity. These studies may reveal a novel post- translational control mechanism that may explain various aspects of thyroid physiology and pathophysiology.