Animal models of tuberculosis infection continue to provide useful information about the nature of the disease process, including specific information about the immune response to the infection and the disease pathology. In addition, standardized animal models are now used extensively to test the capacity of new vaccines to inhibit the course of the infection, as well as test the capacity of new drugs to sterilize the infection. This unit describes some basic protocols illustrating established protocols for infecting animals with tuberculosis, subsequent processes for analysis, and various aspects of biosafety that must be observed. Using these protocols the course of infection, the basic immune response, and the extent of lung pathology can be determined in mouse and guinea pig models of experimental tuberculosis.