The pattern of virus-induced and allergic demyelinating encephalomyelitis in the dog were compared. The predominant pattern of myelin loss in canine distemper (CD) infection was focal, periventricular and was initially noninflammatory. In contrast, sensitization to myelin produced a uniform pattern of central nervous system (CNS) myelinolysis which was disseminated, inflammatory and perivascular. Ultrastructurally, virus-infected neuroglia participated in the demyelination in CD, whereas infiltrating haematogenous mononuclear cells predominated in the lesions of experimental allergic encephalomyelitis (EAE). Areas of predilection within the CNS differed, being influenced by viral spread in CD and by vascular factors in EAE. In CD, the paramyxovirus appears to play a central role in the process of demyelination. In contrast to EAE, however, these studies do not support the view that autoreactivity to myelin contributes to the pathogenesis of CD demyelinating encephalomyelitis.