Histopathological changes in the lung were assessed in a model infection of mice using swine influenza virus and Staphylococcus aureus. Virus preinfection markedly enhanced both the persistence of S. aureus and the extent and duration of the inflammatory response. Lymphocytic infiltration was increased and regeneration and squamous metaplasia were delayed, suggesting an enhancement of an immunopathological response to the virus. Mice with the dual infection showed a decrease in phagocytic cell infiltration of the lung compared to that observed in those with the bacterial infection only, and this may reflect a decline in alveolar macrophage function after influenza infection.