Several lines of rats transgenic for human leukocyte antigen (HLA)-B27 spontaneously develop a multisystemic inflammatory disease resembling human spondyloarthropathies. This disease is mediated by cells of the immune system and is dependent on the presence of a normal bacterial flora. Both antigen-presenting cells expressing high levels of HLA-B27 and T cells appear to be of importance in the pathogenesis of this model. HLA-B27 transgenic/b2- microglobulin deficient mice also develop arthritis, under the influence of the bacterial flora. In both types of model, CD8+ T cells appear to be unnecessary, arguing against the "arthritogenic peptide" hypothesis.