CD8 is a differentiation antigen present on T lymphocytes that recognize antigen together with the class I major histocompatibility complex (MHC)(Swain 1983). There is a growing body of evidence to support the idea that CD8 binds to MHC class I molecules and increases the avidity of T-cell receptors (Tcr) for the target molecule (Norment et al. 1988b, Rosenstein et al. 1989). Interestingly, it has also been shown that Leu-2/T8 is expressed on some natural killer (NK) cells (Lanier et al. 1986) although the degree of expression is less in NK cells than in T cells. Biochemical studies appear to indicate that human CD8 exists only as a homodimer of the a chain (Leu-2/T8) in mature T cells. In rodents, on the other hand, the CD8 molecule has been shown to exist as a heterodimeric form of two glycoproteins (Ly-2 and Ly-3 in the mouse, M r 32 000 and 37 000 glycoproteins in the rat; Ledbetter et al. 1981, Johnson and Williams 1986). Molecular cloning of mouse and rat CD8 molecules has revealed that they all have an IgV-like domain and belong to the Ig-gene superfamily (Nakanchi et al. 1985, Zamoyska et al. 1985, Nakauchi et al. 1987a, Panaccio et al. 1987, Johnson and Williams 1986). It has recently been shown that a gene homologous to mouse (Ly-3) and rat (OX-8, Mr 37 000) genes is also present in man (Johnson 1987). Several groups have reported the isolation of human CD8~ chain cDNA (Norment and Littman 1988a, DiSanto et al. 1988, Shiue et al. 1988). It can accordingly be hypothesized that human CD8 consists of a heterodimer of Leu-2 (c~ chain) and the human homologue of Ly-3 (CD8~ chain). Since a single 13.5 kilobase pair (kb) band was detected with the 1.7 kb Leu-2/T8 cDNA probe (Kavathas et al. 1984) by Southern hybridization analysis of Bam HI-digested human genomic DNA, a size selected Bam HI-digested human genomic library was screened with