A major challenge in influenza research is the selection of an appropriate animal model that accurately reflects the disease and protective immune response to influenza infection in humans. Ferrets are exquisitely susceptible to infection with human influenza viruses and are widely believed to be the ideal small animal model for influenza research. Mice have also been used for influenza vaccine research for decades. Although human influenza viruses generally cause disease in mice only if they are first adapted to the species, the ready availability of mice, their relatively low cost, and the variety of genetic backgrounds and targeted defects, and the immunologic reagents available make the mouse an attractive and heavily utilized animal model for studies of influenza. Although they are not discussed in detail in this unit, hamsters, guinea pigs, cotton rats (Sigmodon), and rats (Rattus) have also been used for influenza research.