Throughout the years, a long list of viruses has been associated with multiple sclerosis (MS), however no virus to date has been definitively identified as the etiologic agent of this disease. Recently, human herpesvirus 6 (HHV-6), a newly described herpesvirus, has been suggested to play a role in MS based on: immunohistochemical demonstration of HHV-6 in MS plaques, increased antibodies response to HHV-6 in sera and CSF of MS patients, and the demonstration of HHV-6 DNA in the serum of MS patients but not in normal individuals. To extend these observations we have focused our research in multiple directions. We have increased the number of MS patients tested for HHV-6 serum DNA providing confirmation of our previous study. Additionally we have investigated a possible correlation between HHV-6 viremia and clinical activity. Finally to provide insight into the pathogenesis of this disease, we have begun to characterize the cellular immune response of MS patients to HHV-6. Collectively these studies will help to define the role that HHV-6 may play in the pathogenesis of MS.