Antibodies against myelin oligodendrocyte antigens have been found in the immunoreactive brain lesions of Multiple Sclerosis (MS) patients. Recently it has been proposed that these antibodies can be used as a prognostic marker in the course of disease. However, the serum levels of these autoantibodies during different phases of disease activity or after an immunomodulatory therapy have been poorly investigated. In this study the serum levels of anti-myelin oligodendrocyte glycoprotein (MOG) (directed against the epitopes 1-26 and 15-40) and anti-myelin basic protein (MBP) antibodies were sequentially measured in the same MS patient either in relapse or remission phases. We found that MS patients in the relapse phase had higher serum anti-MOG (peptides 1-26 and 15-40) and anti-MBP antibody levels than controls. In addition, the levels of anti-MOG 1-26 were also elevated during the relapse as compared with the remission phase but no significant changes were found in the levels of anti-MOG 15-40 of anti-MBP antibodies. We also evaluated the effect of interferon-beta (beta) therapy on anti-myelin antibodies. 1-year of interferon-beta treatment did not induce any changes in the levels of anti-MOG and anti-MBP antibodies. In conclusion, these data indicate that the use of peripheral levels of autoantibodies against MOG and MBP as marker of multiple sclerosis might be complicated by the phase of disease activity and by the epitope of the MOG protein used.