A major factor in the pathogenicity of Newcastle disease virus (NDV) is the amino acid sequence of the fusion protein cleavage site, but the role of other viral genes that contribute to virulence and different clinical forms of the disease remain undefined. To assess the role of other NDV genes in virus pathogenicity, a reverse genetics system was developed using the mesogenic NDV Anhinga strain to provide a backbone for generating gene mutations or gene exchanges in attempts to enhance or attenuate the virulence of that virus. Chimeras created by exchange of the Anhinga Hemagglutinin-Neuraminidase (HN) gene with HN genes of neurotropic and viscerotropic velogenic viruses produced no significant change in virus pathogenicity as assessed by conducting the mean death time and intracerebral pathogenicity index assays and by inoculation of susceptible day-old SPF chickens. Inclusion in the recombinant construct of homotypic F genes, obtained from the parental viruses, also failed to enhance the pathotype of the recombinant viruses to a velogenic pathotype. A HN gene exchange alone within the context of the NDV Anhinga backbone failed to increase virus virulence from mesogenic to velogenic pathotype and suggests a multigenic role for NDV pathogenicity.