The natural reservoir of all known subtypes of influenza A viruses are aquatic birds, mainly of the orders Anseriformes and Charadriiformes in which the infection is asymptomatic and the viruses stay at an evolutionary equilibrium. However, mammals may occasionally contract influenza A virus infections from this pool. This article summarizes: (i) natural infections in mammals including pigs, horses, marine mammals, ferrets, minks; (ii) results from experimental infections in several animal models including mice, ferrets, primates, rats, minks, hamsters and (iii) evidence for the increased pathogenicity of the current influenza A H5N1/Asia viruses for mammals. Several reports have shown that a number of mammalian species, including pigs, cats, ferrets, minks, whales, seals and finally also man are susceptible to natural infection with influenza A viruses of purely avian genetic make up. Among the mammalian species naturally susceptible to avian influenza virus the pig and the cat might exert the greatest potential public health impact. Despite numerous studies in animal and cell culture models, the basis of the extended host spectrum and the unusual pathogenicity of the influenza A H5N1 viruses for mammals is only beginning to be unraveled. Recently, also the transmission of equine influenza A virus to greyhound racing dogs has been documented.