The murine 4F2 molecule is a 125 kilodalton disulfide-linked heterodimeric cell-surface glycoprotein which has been shown to be involved in the processes of cellular activation and proliferation (1). To elucidate the structure, expression, and regulation of the 4F2 molecule, a murine 4F2 heavy chain (4F2HC) cDNA has been isolated and structurally characterized. The murine 4F2HC is a 526 amino acid (aa) type II membrane glycoprotein which is composed of a 75 aa N-terminal intracytoplasmic region, a single hydrophobic putative transmembrane domain, and a 428 aa C-terminal extracellular domain. Comparison with the human 4F2HC cDNA reveals the highest degree of sequence identity within the transmembrane and intracytoplasmic domains. Northern blot analyses have demonstrated that the 4F2HC gene is expressed at relatively high levels in adult testis, lung, brain, kidney, and spleen, and at significantly lower levels in adult liver and cardiac and skeletal muscle. Studies designed to elucidate the pattern of regulation of the murine 4F2HC gene have demonstrated that it is induced during the process of cell activation, but is subsequently expressed at constant levels throughout the cell cycle in exponentially growing cells.