Host resistance (HR) models are used to evaluate the effect of a test article on clearance of an infectious microorganism in order to assess total immunocompetence. HR models serve as biomarkers of net immunological health or immunological well-being. Immunotoxicity can result either in an impaired clearance of an infectious agent, increased susceptibility to an opportunistic microorganism, prevention of immunization, or exacerbation of latent viral infections. The purpose of immunotoxicity testing is to obtain data that is meaningful for safety assessment, and for immunosuppression the major objective is to determine the significance with respect to increased susceptibility to infectious disease. Host resistance models provide the only sure method of examining the influence of test articles on the functional integrity of the immune system and its ability to eliminate pathogenic microorganisms and tumor cells. They provide the means to directly assess the functional reserve of the immune system. Clearance of influenza virus requires an intact and functional immune system that incorporates a cascade of immune responses. Mechanistic studies can be included in the influenza virus host resistance model by measuring the effect of a test article on innate immunity (cytokine and interferon production, macrophage function, and natural killer (NK) cell function) and acquired or adaptive immunity (cytotoxic T lymphocyte (CTL) activity as well as influenza-specific IgM and/or IgG antibody).