The nature of the interactions between cells of the immune system has been shown to be directly related to a group of antigens present on the surface of B lymphocytes. These antigens are under genetic control of the HLA-D/DR region of the human major histocompatibility complex (MHC) located on chromosome 6. DR antigens (the products of the HLA-DR locus within this region), have been defined by serological studies. Recently another antigen, DC-1, has been serologically defined. In the mouse, the I region, analogous to the HLA-D/DR region in man, has been subdivided into at least five subregions (A, B, J, E and C) and specific functions and cell populations associated with each of the subregions. Although in man the HLA-D/DR region cannot at present be subdivided, limited NH2-terminal amino acid sequence data have shown that the DR molecule is homologous to the I-E molecule of the mouse. Furthermore, evidence that DC-1 is not homologous to I-E (and might therefore be homologous to I-A) has been reported. We now report that, using immunoadsorbents prepared with monoclonal antibodies specific for DR or DC-1 antigens, these two human alloantigens were purified from a human lymphoblastoid cell line (LB) and the chains were separated. The NH2-terminal amino acid sequence of the heavy chain of DC-1 antigen shows great structural homology with the murine I-A molecules, thus providing direct evidence of homology of DC-1 to murine I-A.