The enzymes of glycogen metabolism have contributed significantly to our understanding of the molecular basis of enzyme regulation. There are, consequently, a number of reviews of this area, and in particular glycogen synthase (UDP-glucose 4-a-glucosyltransferase, EC 2.4. 1.11) has been quite recently the subject of some rather comprehensive treatments 1'2 which it does not seem profitable to reiterate. Therefore, this article will concentrate on recent developments in the study of glycogen synthase. Since some of the newer findings, and notably the current interest in the multiply phosphorylated subunit, are somewhat provocative with regard to the functioning of synthase in the cell, it is timely to discuss the possible biological implications of multiple phosphorylation. Current considerations of the regulation of glycogen synthase derive from the original observations that the enzyme in muscle could exist in different kinetic forms, distinguishable by their susceptibility to glucose-6-P activation. The first evidence for the interconversion between these two forms came from experiments in which muscle was treated with insulin 3. Shortly afterwards, the changes in kinetic properties were correlated with the phosphorylationdephosphorylation of the enzyme 4. The concept evolved, then, of two distinct species of glycogen synthase. One form, which contained covalent phosphate, would have a very low** an invited article. activity in the absence of glucose-6-P and was termed the D (dependent) enzyme. The other, lacking covalent phosphate and active even in the absence of glucose-6-P, was termed I (independent) enzyme. Table 1 shows a general anticipatory summary of some important properties of glycogen synthase and indicates some of the differences related with phosphorylation of the enzyme. Together with the proposal that the D form of synthase was inactive in viz) o 6, the nature of several hormonal influences on the interconversion of synthase species led to a functional significance for the phosphorylationdephosphorylation of the enzyme. Hormones mobilizing carbohydrate reserves, such as glucagon 7 and epinephrine s, would switch off glycogen synthesis by promoting the abundance of the inactive D form of synthase in liver and muscle. A hormone such as insulin, stimulating glycogen deposition, would turn on synthase by increasing the proportion of the active I form 3. The fundamental validity of this model of hormonal regulation has been verified in many laboratories. Further, the glycogen synthases from a number of sources have been shown to exist in forms differing as to glucose-6-P activation (for listings, see references 1 and 2). This is true even for some organisms lacking classical endocrine control, the enzyme from yeast being the best-studied example. A brief note concerning nomenclature is necessary. Where no confusion arises, we have