Lyt-3 is a membrane glycoprotein expressed on thymocytes and class I major histocompatibility complex-restricted cytotoxic T cells. Lyt-3 is expressed as a heterodimer with Lyt-2, and this complex is considered to be a homologue of the human Leu-2/T8 (CD8) that has been postulated to be a receptor for the class I major histocompatibility complex. We have determined the complete primary structure of Lyt-3 from the nucleotide sequence of its cDNA clones. Analysis of the predicted amino acid sequence indicates that the Lyt-3 polypeptide has a 21-amino acid leader peptide, and the mature protein consists of an NH2-terminal region of 146 amino acids, a transmembrane region of 27 residues, and a C-terminal region of 19 amino acids. The NH2-terminal 110 residues show clear homology to the T-cell receptor and immunoglobulin variable region sequences. In addition, Lyt-3 has 11 residues that have strong homology to the joining region sequences of the T-cell receptor and the immunoglobulin heavy and light chains. The presence of immunoglobulin variable- as well as joining-region-related sequences in Lyt-3 further supports the idea that these molecules may be recognition molecules belonging to the immunoglobulin super gene family.