The CSF from 279 patients with multiple sclerosis (MS), probable MS, or controls was examined by radioimmunoassay (RIA) for antibodies to measles, rubella, mumps, parainfluenza 1 (Sendai) (strain 6/94), herpes simplex (HSV), varicella, and vaccinia viruses. Significantly more patients with MS than noninflammatory control patients had antibody to measles, rubella and varicella viruses, of which antibody to measles was the most prevalent. The percentage of patients with MS with two or more CSF antibodies was significantly greater than that in the controls. There was no tendency for certain antibodies to be associated. There was a general relationship between presence of CSF antibodies and severity of MS. The data support the hypothesis of local CNS antibody synthesis of several viral antibodies; however, such local synthesis may be a random event, possibly dependent on the number and specificity of peripheral virus antibody-forming lymphocytes available for ingress into the CNS.