To clarify mechanisms underlying acute disseminated encephalomyelitis (ADE) in patients with infection due to measles or other viruses, a new animal model was devised. Adult hamsters that had clinically recovered from acute encephalitis induced by prior intracerebral injection of the HBS strain of measles virus were challenged with neuroantigen plus adjuvant. Such hamsters, which had a high likelihood of carrying persistent HBS measles virus in the central nervous system (CNS), exhibited a significantly higher incidence of experimental allergic encephalomyelitis (EAE) following challenge as compared with simultaneously challenged but previously uninfected littermates. Occurrence of EAE in hamsters previously injected with heat-inactivated virus was not potentiated, a finding suggesting that persistence of the virus in the CNS renders that organ system more vulnerable to immunologic attack. This new model has promise for the probing of relationships between persistent viral infections of the CNS and host autoimmune responses directed against that target organ system.