Most studies on H5N1 pathology describe pulmonary features of human disease. Although H5N1 virus infection of humans is primarily one of the lower respiratory tract, more recent reports suggested that influenza A H5N1 may in rare, severe cases, disseminate beyond the lungs and infect brain [26, 27] , intestines [20, 27] and lymphoid tissues [27] , and result in extra-pulmonary clinical manifestations including encephalopathy or encephalitis [15, 28] . This extrapulmonary dissemination of HPAI H5N1 virus contrasts with seasonal influenza virus infection of humans which, even in fatal cases, is restricted to the respiratory tract. However, there have been relatively few reports describing histopathology and virus distribution in H5N1 cases [5, 16, 21, 24, 26, 27] . To better understand the pathogenesis of human H5N1 virus infection, and investigate the route of virus dissemination in vivo, we report on the use of different techniques to detect virus distribution and infection of 5 organ systems in a laboratory confirmed fatal human H5N1 virus infection, and analyze the relationship between viral load in tissues and host response. Our results suggested that the virus can infect multi-organs besides pulmonary. High viral load is associated with increased host response though the viral load is significantly difference in various organs. Cells of immunologic system could not be excluded to play a role in dissemination of the virus.