The cDNA for mouse brain glycogen synthase has been isolated by screening a mouse cerebral cortical astrocyte lambda ZAP II cDNA library. The mouse brain glycogen synthase cDNA is 3.5 kilobases in length and encodes a protein of 737 amino acids. The coding sequence of mouse brain glycogen synthase cDNA shares approximately 87% nucleotide identity and approximately 96% amino acid identity with the muscle isozyme, while the degree of identity is lower with the liver isozyme. The regional distribution of glycogen synthase mRNA determined by in situ hybridization in the mouse brain reveals a wide distribution throughout the central nervous system with highest densities observed in the cerebellum, hippocampus and olfactory bulb. At the cellular level the expression of brain glycogen synthase mRNA is localized both in astrocytes and neurons with, however, the higher levels observed in astrocytes. Vasoactive intestinal peptide and noradrenaline, two neurotransmitters previously shown to induce a glycogen resynthesis in cultured astrocytes, upregulate the expression of glycogen synthase mRNA in this cell type but not in neurons.