The development of a transgenic mouse model carrying the human poliovirus receptor has made it possible to investigate the molecular mechanisms of the viral dissemination process in a whole organism. Studies on this have provided an insight into the mechanisms for viral permeation through the blood-brain barrier and retrograde axonal transport of the virus. In addition, strain-specific neurovirulence levels are shown to depend mainly on the replicating capacity of the virus in the central nervous system rather than the efficiency of the 2 dissemination pathways indicated above. Studies of poliovirus-induced cytopathic effects on neural cells revealed that neural cells possess anti-poliovirus characteristics that may offer a new avenue for investigating the molecular mechanisms of poliovirus neurovirulence.