Mouse cytomegalovirus (MCMV) is a well developed and extremely useful and relevant host resistance model for immunotoxicity testing. Rat cytomegalovirus (RCMV) is currently under development and may have similar applications. Cytomegaloviruses are species specific; RCMV is a distinct virus from MCMV and both are distinct from human cytomegalovirus (HCMV). However, biologic and biophysical similarities between these viruses make the animal viruses good models for the human infection. The chapter discusses the rationale for using MCMV as a host resistance model, provides some representative data, and gives detailed information on methods needed to apply the model. Background on RCMV is also presented along with detailed methods (to the extent available) for applying the RCMV model are also provided.