The mouse-adapted Lansing strain of poliovirus type 2 PV-2(L) induces fatal poliomyelitis in mice after intracerebral inoculation, while mice inoculated with Mahoney strain of poliovirus type 1 PV-1(M) show no signs of disease. Previous work had indicated that both the 5' non-translated region of the viral genome and the viral capsid protein, neutralization antigenic site I (N-Ag1), were involved in mouse neurovirulence. In order to further explore the role of N-Ag1 in mouse neurovirulence, antigenic chimeras of two poliovirus strains, XF414 and XF324, were constructed. In the two strains, ten amino acids (in XF414) or 16 amino acids (in XF324) in antigenic site I in Vp1 of PV-I (M) were replaced with a PV-2(L)-specific sequences using a mutagenesis cartridge. Mouse neurovirulence tests indicated that mice cerebral inoculated with XF414 and XF324 developed poliomyelitis leading to paralysis or death. The viruses possessing antigenicity of the inoculating viruses were isolated from cerebral tissues of the paralyzed mice. The results demonstrated that N-Ag1 is an important determinant of poliovirus host range, and may be involved in attachment and penetration of poliovirus (in)to cells of the mouse central nervous system.