Humans who have inherited the human class I major histocompatibility allele HLA-B27 have a markedly increased risk of developing the multi-organ system diseases termed spondyloarthropathies. To investigate the role of 827 in these disorders, we introduced the 827 and human BP-microglobulin genes Into rats, a species known to be quite susceptible to experimentally induced inflammatory disease. Rats from one tranagenic line spontaneously developed inflammatory disease involvlng the gaatminteatinal tract, peripheral and vertebral joints, male genital tract, akin, nails, and heart. This pattern of organ system involvement showed a striking resemblance to the B27-aaaociated human disorders. These results eatabllah that 827 plays a central role in the pathogeneala of the multi-organ system processes of the apondyloarthropathiea. Elucidation of the role of 827 should be facilitated by this tranagenic model.