Vertebral ankylosing hyperostosis is a common skeletal disorder among Pima Indians. Prevalence rates of approximately 50% have been reported in Pima Indian males aged 44 or older. The HLA-B27 antigen is also found more commonly in Pima Indians than in Caucasians (18% versus 6%). Because of the increased prevalence of both vertebral ankylosing hyperostosis and HLA-B27 in Pima Indians, a possible association between the two was thought to exist. Therefore, histocompatibility testing was done on 44 adult male Pima Indians age 55 or older with classic vertebral ankylosing hyperostosis and 33 age-matched controls. No significant association between any histocompatibility antigen phenotype or haplotype and vertebral ankylosing hyperostosis was found. This disease, therefore, connot be classified with the HLA-B27 associated spondylarthropathies.