This review focuses on investigations of rats and mice transgenic for HLA-B27; these animals have been investigated for several years as potential models for the human spondyloarthropathies. Spontaneous multisystem disease occurs in rats with high expression of B27 and human beta2-microglobulin (hbeta2m). The disease is T-cell-dependent and is sensitive to both environmental and genetic manipulation. A spontaneous arthritis and enthesopathy has been observed by some investigators in nontransgenic mice which seems to be more prevalent in B27 transgenic mice. Peripheral arthritis has also been reported in B27 transgenic mice that lack mouse beta2m. Potential insights from these animals into the pathogenesis of B27-related disease are discussed.