Behcet’s disease is a chronic inflammatory disease with unknown etiology. Association with anti-endothelial cell antibody(AECA) has been explored since vascular involvements such as vasculitis, thrombophlebitis, or thrombosis can be observed in Behcet’s disease. Also, AECA was detected in the sera of Behcet’s disease patients. Our previous experiment identified α-enolase as the target protein of AECA in the sera of Behcet’s disease patients by proteomics technique. Streptococcus and autoimmune reaction to oral mucosal antigen have been suggested as the causes of oral ulceration in Behcet’s disease. This study tried to elucidate the association between Streptococcus sanguis(or Streptococcus sanguinis) antigen and anti α-enolase antibody(AAEA). Forty two patients with Behcet’s disease diagnosed at the Behcet’s Disease Special Clinic in Severance Hospital and ten healthy individuals were included in this study. Reaction between anti human α-enolase antibody purified from the sera of the patients and Streptococcus sanguis cell wall antigen were measured by ELISA. Analysis revealed that absorbance in Behcet’s disease patient group was stronger than that in normal control group with statistical significance. Sera from the patients with strong reaction to α-enolase also showed strong reaction to Streptococcus sanguis antigen. Moreover, AAEA used as positive control also showed strong reaction to Streptococcus sanguis antigen. Further 2-D analysis of Streptococcus sanguis protein revealed streptococcal α-enolase as the target protein of AAEA. Therefore, we suggest the possibility of cross-reactivity of anti human α-enolase antibody to Streptococcus sanguis antigen.