Because HLA-B27 is such an important genetic marker for susceptibility to spondyloarthropathies and other related diseases, study of this alloantigen was undertaken using murine monoclonal antibodies. The first monoclonal anti-B27 antibody, B27M1, is an IgG2a lymphocytotoxic antibody that reacts with all B27 antigens and cross-reacts to a lesser degree with the B7 antigen. Cross-reactivity with B7 is attributed to a B27-like epitope on the B7 antigen but which, as determined by cytotoxicity blocking studies, is distinct from the B7 allospecific epitope itself. The second B27 monoclonal antibody, B27M2, is a lymphocytotoxic IgM antibody reacting with most (greater than 85%) but not all of B27 antigens tested and having no cross-reactivity with B7. As determined by cytotoxicity blocking studies, the B27M2 epitope appears near the allospecific B27 epitope and the B27M1 epitope on the B27 antigen molecule. Immunochemical studies reveal isoelectric point and size differences between the B27M2+ and the B27M2- variants of HLA-B27. Based on these data, a model is proposed for the B27 antigen in which a B27M1 epitope is constant but the B27M2 epitope is present on the B27 antigen of some individuals and absent from that of others. B27M1 antibody reactivity does not appear to be associated with unusual disease susceptibility but preliminary data suggest the B27M2- variant of B27 may be more strongly associated with ankylosing spondylitis.