Most autoimmune diseases are associated with certain HLA types. Therefore, spondyloarthropathies (SpA) strongly associated with HLA-B27, are also often classified as autoimmune diseases. This study questions whether SpA indeed fulfils the criteria of an autoimmune disease. The Medline database was searched for all reports between 1966 and April 1998 on the presence of autoimmune reactivity in SpA patients. This search yielded 45 articles on this subject. Only eight articles study T cell reactivity. Twelve reports were found on the assessment of antibodies crossreacting between bacteria and HLA-B27. In the 45 studies demonstrating autoimmune reactions in SpA patients proper controls matched for HLA-B27, sex and age were nearly always lacking. Therefore, it is concluded that the frequency of increased autoreactivity in sera from patients and controls is not significantly different, and that this lack of autoreactivity does not justify classification of SpA as an autoimmune disease. As crossreactive antibodies against bacteria and HLA-B27 were equally present in sera from patients and controls, the pathogenetic significance of molecular mimicry between various bacteria and HLA-B27 is questionable. Furthermore, the regions of the B27 molecule that are supposed to be crossreactive with bacteria, differ in one or more amino acids among the distinct B27 subtypes. Although these differences strongly influence the binding of antibodies to the B27 molecule, there was no relation between the degree of crossreactivity of certain subtypes and the association of these subtypes with SpA. In conclusion, there is no evident proof that SpA is an autoimmune disease attributable to crossreactivity between bacteria and HLA-B27.