As heat shock proteins (HSPs) are described as candidate self-antigens in Behçet's disease (BD), free HSP70 and anti-HSP70 levels were measured in the sera of patients to investigate their role in the pathogenesis of BD.Free human HSP70 levels were measured in the sera of patients with BD and compared to disease controls [patients with rheumatoid arthritis (RA) or recurrent oral ulcerations (ROU)] and healthy controls (HC) using ELISA. Anti-HSP70 antibody levels were also determined.Free human HSP70 levels were significantly elevated in BD sera (1.12+/-0.86 ng/ml) compared to HC (0.67+/-0.46 ng/ml, BD vs. HC: p<0.001). However similarly elevated levels were also present in ROU (0.95+/-1.01 ng/ml, p<0.05) and RA (1.1+/-23.3 ng/ml, p<0.01). Anti-HSP70 antibody levels were also significantly higher in BD (668+/-658 microg/ml) compared to HC (490+/-742.05 microg/ml, p<0.05). However no significant anti-HSP70 antibody responses were observed in ROU (634.7+/-548.21 microg/ml) and RA (431.8+/-840.98 microg/ml). No association of any organ manifestation, the disease duration, or treatment with HSP70 or anti-HSP70 antibody levels were observed in BD. A correlation between HSP70 and anti-HSP70 levels was only found in HC (p=0.007).Free human HSP70 and anti-HSP70 antibodies are both elevated in patients with BD. HSP70-mediated innate and adaptive immune responses may participate in proinflammatory cytokine activation and tissue destruction in BD.