When studying heterogeneity of B27-positive disease versus B27-negative disease, very different patterns of disease associations but also a lot of similarities may be observed. In general, B27-positive disease has an earlier onset, a more severe and prolonged clinical course and is more often complicated by acute anterior uveitis and peripheral arthritis, whereas B27-negative disease is accompanied by psoriasis, inflammatory bowel disease and erythema nodosum in a higher percentage of the cases. Despite these differences, B27-positive disease may be completely undistinguishable from B27-negative disease in a number of individual cases. Family aggregation and male preponderance, however, are only seen in B27-positive disease. These observations may lead to the conclusion that HLA-B27 is probably not the only key to the pathogenesis of these diseases, but nevertheless an important genetic factor in disease expression.