A mouse model study using mouse brain‐adapted influenza A virus was performed to establish the prophylaxis and treatment of influenza encephalitis and encephalopathy. All mice died after intranasal inoculation of the brain‐adapted influenza A virus (H7N3), and the pathological findings indicated the presence of significant encephalitis. Viral antigen was also detected in the brain, both pathologically and virologically. By contrast, infected mice immunized with inactivated vaccine of the same strain did not lose weight, which is an indicator of the overall condition of the mice, and all of them survived. Similarly, antiserum treatment in the early period (0–1 day post‐infection) resulted in 100% survival, and no pathological findings were observed in the brain. However, mice treated with antiserum 3 days post‐infection showed encephalitis with viral antigens in both glial cells and neurocytes. Although amantadine treatment for 4 days delayed weight loss, it did not prevent death from encephalitis. These results show vaccination and early antiserum treatment to be highly effective, whereas 4‐day treatment of amantadine was not very effective in treating or preventing influenza encephalitis. The life‐prolonging effect of amantadine, however, suggests that use of amantadine together with other treatments may inhibit the progression of encephalitis. J. Med. Virol. 67:406–417, 2002. © 2002 Wiley‐Liss, Inc.