The distribution of canine distemper virus (CDV) antigen was examined in the brains of 14 dogs with chronic nervous distemper using a monoclonal antibody against a major viral protein. In ten of these dogs, neutralizing anti-CDV antibody titers were determined in serum and unconcentrated cerebrospinal fluid (CSF). In 19% of the inflammatory demyelinating lesions, large amounts of CDV antigen were found; in 34% of these lesions only residual traces of virus were seen and in almost half of the lesions (47%) no CDV could be demonstrated. In four dogs neutralizing antibodies were found in the serum only; in one dog in the CSF only and in 5 dogs both in serum and CSF. Because of the correlation between the presence of inflammation, intrathecal antiviral antibodies and disappearance of CDV from the lesions, it was concluded that the inflammatory response in distemper is associated with viral clearance from the lesions. Associated immune-mediated cytotoxic reactions could explain exacerbation of the initial virus-induced demyelinating lesions. Despite the presence of an apparently effective intrathecal antiviral immune response, fresh non-inflammatory lesions as a result of viral replication and spread in the white matter coexisted with inflammatory ones in which viral clearance had taken place. The role and mechanism of such virus persistence are discussed.