Abstract: Objectives: The etiology and pathogenesis of Behcet's disease (BD) are still unknown. It seems that in a special genetic background exogenous or endogenous antigen(s) acts as trigger in up regulating and presenting the pathogenic epitope. The immune system reacts in an abnormal way, by inducing a cascade of cytokines and chemokines to stimulate innate immune responses, leading to the lesions of the disease. Genetic background: The major susceptibility gene is the HLA-B51 allele itself, though there is little evidence for its pathogenecity. The increase of MICA (MHC class I chain-related gene A) alleles (6 and 9) in BD patients is secondary to the linkage disequilibrium with B51. Antigen: Some exogenous or endogenous antigen(s) such as bacteria (streptococcal strains), herpes simplex virus, or host cross-reactive mucosal antigens may trigger the BD onset. A common denominator to these agents might be the heat shock protein (HSP). Specific immune responses in BD were found to be stimulated by shared epitopes within human 60-kD HSP (peptide 336-351) and mycobacteria165-kD HSP. Altered immune response: It has been suggested that ү/б T cells play an essential role in the immunopathogenesis of BD. Stimulation of ү/б T cells with microbial HSP or their constitutive peptides coupled with the capacity of MICA gene product to present peptides to them, enhances the significance of ү/б T cells in BD. The weight of evidences is in favor of a TH1 type response in BD. PMN hyperfunction is one of the most characteristic features in BD. PMN are capable of promoting their own recruitment, the production of pro-inflammatory cytokines and of 02 free radicals (which seems to be B51 related). Cell adhesion molecules are essential for PMN to reach the involved tissue, while TNF-α helps the accumulation by reducing the PMN spontaneous apoptosis.