There have been many attempts to isolate infectious agents from patients with multiple sclerosis (MS), and many viruses have been incriminated at one time or another over the past few decades. However, in every case further research has disproved the original claim. Thus, we cautiously report on the isolation of four antigenically related agents from the cerebrospinal fluid (CSF) of three patients with MS and one patient with amyotrophic lateral sclerosis. The patients yielding the isolates from their CSF possessed neutralizing antibodies to the virus in their blood, in contrast to several other virus-free patients with chronic central nervous system (CNS) diseases studied at the same time. The virus could not be isolated from 27 patients who were not suffering from chronic disease of the CNS. The agent has not yet been adequately characterized, but it deserves further attention because it seems to be a hitherto unknown virus, difficult to isolate and difficult to work with in the laboratory. Its isolation from the four patients mentioned above (and subsequently in several other MS patients) warrants further investigation of its potential role in MS and other progressive diseases of the CNS.