Objective. To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behqet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behqet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice, Methods. Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichlorofluorescein, induced by superoxide in the neutrophils.Results. A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-BS1 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide.Conclusion. The HLA-BS1 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behqet's disease.