By using neonatal gerbils, we assessed the effect of ribavirin on the proliferation of Borna disease virus (BDV) in the brain. The intracranial inoculation of ribavirin reduced viral propagation in the acutely infected brain, resulting in protection from fatal neurological disorders. We found that the treatment with ribavirin markedly reduces the numbers of OX-42-positive microglial cells, but does not activate expression of Th1 cytokines, in BDV-infected gerbil brains. Our results suggested that ribavirin directly inhibits BDV replication and might be a potential tool for the treatment of BDV infection. (C) 2008 Elsevier B.V. All rights reserved.