Background: Multiple sclerosis (MS) is the most common autoimmune disease of central nervous system with destruction of myelin sheath mediated by auto reactive CD4+T Lymphocytes. Because of the possible role of Epstein-Barr virus in etiology of MS and T cells immune response, the aim of this study was to evaluate anti-Epstein Barr virus antibodies as a marker of reactivity and production of TH1 and TH2 cytokines in MS patients and healthy individuals.Methods: Blood samples were taken from 68 MS patients at different stages of diseases and 20 apparently healthy individuals and plasma levels of anti- EBV nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) antibodies determined and concentrations of IFN-, IL-12 and IL-4 in culture supernatants of PHA-activated peripheral blood mononuclear cells (PBMC) were measured by ELISA.Results: The mean levels of anti EBNA-1 and VCAantibodies were significantly higher in patients compared to controls (p=0.04, p=0.001 respectively). Concentrations of IFN-, IL-4 & IL-12 were also significantly higher in MS patients than healthy individuals (p=0.001, p=0.005, p=0.002, respectively). Significant correlation was found between anti EBNA-1 and VCAantibodies and IL-12 production (p=0.02, r=0.27 & p=0.04, r=0.25, respectively); whereas no significant correlation was found between these antibodies and production of IFg-or IL-4.Conclusions: Due to elevated level of anti-EBV antibodies and T cell Cytokines in MS patients Rather than healthy individuals, Epstein Barr virus may play role in etiology of MS disease through activation of T cells immune response.