Multiple sclerosis (MS) is a serious chronic neurological disorder in which demyelination and inflammation occur in the white matter of the CNS. The findings of many epidemiological studies and a discordance of MS in monozygotic twins suggest that the disorder is acquired. The most likely cause is a virus because more than 90% of patients with MS have high concentrations of IgG, manifest as oligoclonal bands, in the brain and CSF. Most chronic inflammatory CNS disorders are infectious. More indirect evidence that MS is caused by a virus is the association of several viruses with demyelinating encephalomyelitis in human beings, and the induction of demyelination in animals infected with viruses in research. Nevertheless, no virus has been isolated from the brains of patients who had MS. Molecular analysis of IgG gene specificity in the brain and CSF of those with MS has shown features of an antigen-driven response: clonal amplification and extensive somatic mutations. A viral antigen against which the IgG in MS brain and CSF is directed might be identified.