Neurovirulence in mice is a unique property of some influenza virus strains including NWS and WSN strains. We performed clinical and immunohistochemical studies on mice after intracerebral inoculation with the neurovirulent WSN. On day 3 after inoculation, WSN antigen was detected in meningel and ependymal areas, neurons of circumventricular regions, the cerebral cortices, the substantia nigria zona compacta and the vental tegmental area. On day 7, advanced accumulation of the viral antigen was evident in the substantia nigra zona compacta and hippocampus. Double immunostaining demonstrated that the WSN antigen was only seen in neurons and not in microglia or reactive astrocytes. The responsible genes for neuro virulence were summarized.