The highly pathogenic avian influenza, H5N1 subtype, has been transmitted to humans in 15 countries in the world, with a significantly high fatality rate. The transmission to humans has been expanded. Since the virus was transmitted to humans for the first time in Hong Kong in 1997, the transmission of the virus from human to human has been limited. One of the reasons of the limitation can be found in the fact that the sialoglycoconjugates receptor-binding specificity of H5N1 virus is avian-type, and a mutation of the virus for acquiring receptor-binding specificity exclusively to humans has not occurred. However, it is concerned that if such a mutation of the virus occurred, a pandemic of highly pathogenic avian influenza would break out with a scale far exceeding that of the disastrous Spanish influenza in the past. This paper deals with the present condition of the highly pathogenic avian influenza virus, the mechanism of the virus to acquire the propensity of transmissibility to humans, and the measures against such a mutation.