Every HLA antigen, as defined by the WHO-HLA Nomenclature, is unique. The major function of these molecules is to present antigen-peptides to the T-cell receptor, thereby contributing to the immunological defence mechanism. This function is regulated for each MHC antigen by its unique structure, with the peptide-binding pockets of the three-dimensional groove of the corresponding molecules playing the critical role. However, HLA-B27 is special by virtue of its disease association(s). Various aspects which might provide an explanation for--or at least a clue to an understanding of the specific role of--B27 in its disease associations are reviewed. Since it appears that there are no published experimental data which would support either of the alternative hypothetical possibilities, the bulk of current theories must therefore be purely speculative. The only lead to a better understanding of the function of B27 in disease associations is the postinfectious reactive arthritis. If it is the B27 molecule itself which is involved, further in vivo work on B27 transgenic animals might help solve this problem with its numerous unknown factors.