The marked virulence of the 1997 outbreak suggests that infl uenza A (H5N1) infection may have novel pathogenic mechanisms not seen in human infl uenza strains. To attempt to understand pathogenicity of this virus, an infl uenza virus bearing all 8 gene segments of the 1918 pandemic virus, which claimed at least 20-40 million lives, was recently generated in cultured cells. The reconstructed 1918 infl uenza viruses displayed accelerated activation of host immune response in mice with high levels of chemo-kines and cytokines in the lungs, resulting in infi ltration of infl ammatory cells and extensive damage to the lungs with severe hemorrhaging (36) . The pathogenicity induced by the reconstructed virus showed marked similarity to that reported with infl uenza (H5N1).