Two H5N1 viruses isolated in Hong Kong during the 1997 outbreak were found to readily infect ferrets (Zitzow et al., 2002). Since then, more H5N1 isolates that are highly pathogenic for birds have been found to replicate in ferret lungs without prior host adaptation. The infections generally have been characterized by severe lethargy, fever, weight loss, transient lymphopenia, and virus replication in the upper and lower respiratory tract and in multiple organs including the brain. More importantly, the illness induced by these agents was more severe than that induced by recently isolated human H3N2 viruses. The lungs of H5N1-infected ferrets showed diffuse inflammation of interalveolar septa with infiltrates of mononuclear cells and intra-alveolar edema, regardless of the time post infection; in contrast to the scattered infiltrates seen with other influenza A viruses, these changes were observed throughout the lungs (Maines et al., 2005). Viral antigens were detected in alveolar bronchial cells or bronchioles in the majority of animals by day 3 post virus exposure. Brain tissues showed mononuclear cell infiltrates in the meninges, choroid plexus, and brain parenchyma, and viral antigens were detected in neurons in the same areas.