We have studied the distribution of the different HLA-B51* alleles among patients with Behçet's disease (BD) and ethnically matched healthy controls in a Spanish population. The serological B51 specificity was increased in BD patients (37.5% versus 15.5% in controls). Among the B51-associated alleles, the frequencies of B*5101 (32%) and 5108 (5.5%) were increased in BD patients with respect to the control frequencies (13% and 1.2% respectively). The fact that different HLA-B51 subtypes are associated with BD could suggest that common motifs shared by HLA-B51-related alleles are involved in the susceptibility to BD or, in the light of recent studies, that a mutation causing the susceptibility to BD occurred in the B*5101 haplotype, close to HLA-B gene, before the divergence of B*5108 from the B*5101 allele.