As glycogen synthase is a key enzyme of the non-oxidative pathway of glucose metabolism in the skeletal muscle, and reduced activity of this enzyme is related to insulin resistance, it seems likely that this enzyme is a candidate gene for contributing to the pathogenesis of NIDDM. In this paper, we review recent findings of polymorphism of the human glycogen synthase gene, XbaI restriction enzyme length polymorphism and simple tandem repeat DNA polymorphism, and discuss the possible association between the glycogen synthase gene and NIDDM.