Worldwide pandemics of human influenza virus caused extensive morbidity and mortality around the world had been documented in the 20th century. However, the mechanisms involved in the emergence of novel influenza virus and the epidemiological factors leading to pandemics are unpredictable. Southern China is postulated as the epicentre of influenza epidemics due to its agricultural-based communities and high population density. Pandemic influenza viruses are through to arise from avian viruses through genetic reassortment among influenza viruses. An influenza virus (H5N1) known to infect only birds previously was found to infect human causing disease and death in Hong Knog in 1997 and the outbreak involved 18 patients with six deaths. Prior to the human outbreak, the H5N1 virus was found to cause extensive death in chickens in three farms in Hong Kong. The significance of this outbreak raised worldwide concern on the possibilities that such an influenza virus may become the next influenza pandemic strain. Investigations were initiated to find the source of the virus. In addition the extend of spread in individuals in contact with the index case and infected poultry was studied by H5-specific serology. Results demonstrated that individuals in close contact with the index case or with exposure to poultry were at risk of being infected. Out of the 18 cases of human infection, eleven had severe infection with symptoms of pneumonia and multi-organ failure. All severe cases presented with lower respiratory infection and lymphopenia and six eventually died. Case-fatality ratio was high among patients over 12 years of age (five out of nine). Control measures aimed at reducing exposure of human to potential H5-positive poultry were instituted which included culling of all poultry in Hong Kong, the segregation of water fowls and chicken, and the introduction of import control measures for chickens. Such measures had successfully controlled the outbreak and continuous surveillance of the poultry in Hong Kong of H5N1 infection is maintained to minimize future human exposure.