Seventeen avian species and two mammalian species were intranasally inoculated with the zoonotic A/chicken/Hong Kong/220/97 (chicken/HK) (H5N1) avian influenza (AI) virus in order to ascertain a relative range of susceptible hosts and the pathobiology of the resultant disease. A direct association was demonstrated between viral replication and the severity of disease, with four general gradations being observed among these species. These gradations included the following: 1) widespread dissemination with rapid and high mortality, 2) neurological disease relative to viral neurotropism, 3) asymptomatic infection or only mild transient depression associated with minor viral replication, and 4) absence of disease relative to minimal to no viral replication. This investigation not only demonstrates that the chicken/HK virus could infect multiple avian species, but also that the virulence of the chicken/HK virus varied significantly among avian species, including those species that are members of the same order.