A study was performed to determine whether persistent or latent viruses are reactivated during the acute attack in relapsing remitting multiple sclerosis (MS). DNA of herpes simplex virus type 1 and 2 (HSV‐1 and ‐2), human cytomegalovirus (HCMV), Epstein‐Barr virus (EBV), JC virus (JCV) and HTLV‐I was searched, using nested polymerase chain reaction (PCR), in peripheral blood mononuclear cells (PBMCs) collected from 14 MS patients on the first day and, twice a week, during an acute attack of the disease. Results ‐Viral DNA was detected, in at least one PBMC sample, in all the patients. Interestingly, EBV DNA was found in 42.8% of the patients on the first day, while a sharp increase of the HTLV tax‐rex DNA frequency (35.7%) was observed on the tenth day. In MS relapse EBV DNA detection is an early, frequent event, while the finding of tax‐rex, but not of other HTLV‐I genomic regions, is a secondary phenomenon, suggesting that these two factors could interact in the pathogenesis of MS relapses.