HLA-B27 is a serologic specificity that encompasses 20 different alleles-HLA-B*2701 to B*2720. These alleles are also called subtypes of HLA-B27, and they have evolved from the B*2705 subtype, mostly from changes in exons 2 and 3 (which encode the alpha 1 and alpha 2 domains of the peptide binding groove, respectively). Occurrence of ankylosing spondylitis (AS) or related spondyloarthropathy (SpA) has thus far been documented in subjects possessing any one of the first 10 subtypes. However, B*2706 in Southeast Asian and B*2709 in the Italian island population of Sardinia may have a relatively much weaker association with AS. The 10 most recent subtypes have not yet been studied for disease association. There may exist a hierarchical ranking, resulting, in part, from differences in other co-inherited genetic factors, or due to environmental factors; eg, B*2705 is clearly disease-associated throughout the world, but not among the West Africans of Senegal and Gambia. It is important to investigate whether certain subtypes show any preferential association with some of the clinical features or forms of AS and related SpA among the various ethnic/racial populations and geographic regions of the world. This may help to identify the polymorphic positions of HLA-B27 that may have a disease-predisposing role.