Among the proteins encoded by the major histocompatibility complex (MHC) are the highly polymorphic class I major transplantation antigens, HLA-A and HLA-B in man and H-2K and H-2D in mouse. Class I loci also include the less polymorphic HLA-C in man and H-2L in mouse. Class I antigens are 45,000-molecular weight (Mr) glycosylated membrane proteins associated on the cell surface with apparently nonpolymorphic β2-microglobulin1. Linked to the murine MHC are genes encoding the class I-like Qa and Tla antigens, which are closely related structurally to H-2K, D and L, as they are also 45,000-Mr cell surface glycoproteins associated with β2-microglobulin 2-7. Such class I molecules have also been found on the surface of human T lymphocytes8-11 and, in one case, shown to be linked to HLA-A12. Recombinant DNA techniques have been used to map DNA fragments to the Tla region in mouse13,14. A similar genetic analysis of the HLA complex is hampered by the lack of congeneic strains and by the small number of intra-MHC recombinants in well studied families. One means of overcoming these problems involves a molecular genetic analysis of human lymphoblastoid cell line (LCL) mutants15 having γ-ray-induced physical deletions of HLA DNA to map DNA fragments in the MHC16. Here we have applied this method to provide evidence that some human class I-like DNA sequences are telomeric to the A2 locus in LCL 721.