This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (1) basic techniques for mouse infection, tissue sampling, and preservation, (2) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow‐cytometry, and (3) lung histology, immunohistochemistry, and in situ hybridization. Curr. Protoc. Cell Biol. 43:26.3.1‐26.3.28. © 2009 by John Wiley & Sons, Inc.