To characterize the antibody response to the Epstein-Barr virus (EBV) in MS, we studied serum anti-EBV nuclear antigen (anti-EBNA) and anti-EBV capsid antigen (anti-EBVC A) titers. Both titers were assayed in 93 age- and sex-matched pairs of MS patients and controls. Anti-EBVCA titers were measured by indirect immunofluorescence and anti-EBNA titers by anticomplement immunofluorescence. The seropositivity rate of both anti-EBVCA and anti-EBNA in MS patients was l00%, compared with 84% in controls (p < 0.0001). Both anti-EBVCA and anti-EBNA titers were significantly higher in MS patients than in controls (p < 0.0001). The data suggest that EBV has a significant seroepidemiologic association with MS, but they do not define what role EBV antibodies play in the pathogenesis of the disease.