The specificity of antigen presentation by HLA-B27 and its modulation by subtype polymorphism can be understood from knowledge of the three-dimensional structure of this molecule and from biochemical analysis of bound peptides. These studies reveal the basis for the sharing of T cell determinants that might be critical to linkage of multiple subtypes to spondyloarthropathies. The mechanism of this association remains unknown, but involvement of T lymphocytes and HLA-B27 on antigen-presenting cells appears likely. Thus, a direct link between peptide presentation by HLA-B27 and its role in disease is emerging.