The pathogenesis of infection with influenza A virus in mice was studied by exposure of specific pathogen-free mice to aerosols of influenza virus and by monitoring of mortality, viral titers in lung homogenates, and presence of viral antigens in respiratory cells as determined by immunofluorescence. In two experiments with different death rates (100% and 43%), viral antigen accumulated in the epithelial cells lining the airways, in alveolar macrophages, in alveolar cells, and in visceral pleura. By enumeration of the number of airways, alveolar macrophages, and alveolar cells containing influenza viral antigens at different intervals after exposure to the viral aerosol, it was determined that viral replication occurred initially in the epithelial cells lining the airways and later extended to the alveolar macrophages and alveolar cells. This semiquantitative survey of the dynamics of influenza viral infection by aerosol indicated that the viral infection in mice was a descending process.