Intranasal instillation of virus in a liquid suspension (IN) is the most frequently employed method to inoculate small mammalian models with influenza virus, but does not reflect a natural route of exposure. In contrast, inoculation via aerosol inhalation (AR) more closely resembles human exposure to influenza virus. Studies in mice have yielded conflicting results regarding virulence induced by virus inoculated by these routes, and have not controlled for potential strain-specific differences, or examined contemporary influenza viruses and avian viruses with pandemic potential. We used a whole-body AR inoculation method to compare infectivity and disease progression of a highly pathogenic H5N1, a low pathogenic H7N9, and a 2009 H1N1 virus with traditional IN inoculation in the mouse model. Generally comparable levels of morbidity and mortality were observed with all viruses examined using either inoculation route, indicating that both IN and AR delivery are appropriate for murine studies investigating influenza virus pathogenicity.