In none of the rheumatic diseases has the genetic contribution to pathogenesis been so well characterized as in the seronegative spondyloarthropathies. Most important has been the elucidation of the structure and effect on disease expression of HLA-B27, where 11 subtypes have been distinguished to date. These vary in frequency in different ethnic groups and seem to show differential disease associations. The high frequency of this gene in patients with the seronegative spondyloarthropathies, especially ankylosing spondylitis (AS) and Reiter's syndrome (RS)/reactive arthritis (ReA), has emerged as probably the best example of a disease association with a hereditary marker. Other HLA genes, in addition to HLA-B27, have been implicated in psoriasis and psoriatic arthritis. These include those from the HLA-C locus and from HLA-DR. In addition, recent family studies have implicated other genes outside the MHC that further enhance the susceptibility to AS.