We conducted a study of 145 persons with multiple sclerosis who had been identified in a 1970 survey and 145 friend controls, to investigate whether the development of MS was associated with exposure to uncommon viruses or an older age at infection with 1 or more common viruses. The most striking finding was a strong positive association for history of infectious mononucleosis (IM), suggesting older age at exposure to Epstein-Barr virus, the most common etiologic agent of IM. We also found significant positive associations for number of different domiciles before adulthood and for visits outside the United States; both would be compatible with an increased likelihood among cases of exposures to uncommon viruses or to multiple strains of a common agent. Cases were younger at menarche, increasing the probability of viral exposure after puberty.