Although the etiology of Behçet’s disease (BD) is poorly understood, the number of BD patients registrated with the Ministry of Health, Labor, and Welfare is still increasing and it reached almost 18,000 in 2002. Epidemiologically, the prevalence rate of BD patients worldwide is estimated to be high in Middle-Eastern countries and the districts along the “Old Silk Road” to China, Korea, and Japan. More than 60% of BD patients are reported to have HLA-B51 in their genetic background. There are some etiological hypotheses for BD, including virus infection, bacterial infectious allergy, and abnormal immunological phenomena including autoimmunities, etc. Recently, however, streptococcal infectious allergy associated with various immunoabnormalities which induce 65kDa of heat shock protein (HSP-65) and HSP-60 in the sera of the patients has been pointed out as an important factor in BD pathogenesis. Herein, I would like to introduce the recent study trends and our experimental results showing that Streptococcus (S.) sanguis (uncommon KTH-1 selotype) DNA gene (Bes-1) was found in the BD lesions (aphthous and genital ulcerations, perifoliculitis and erythema nodosum-like eruptions) by polymerase chain reaction (PCR) method PCR-in situ hybridization (ISH) revealed the presence of Bes-1 in the endothelial cells and macrophages that had infiltrated into the lesions. The results suggest that S. sanguis from the infectious foci of the patients’ oral cavity might play an important role in the pathogenesis of BD.