Strong cation exchange MRM: Multiple reaction monitoring assay SELDI: Surface-enhanced laser desorption/ionization IMAC: Immobilized metal affinity capture. A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo. Influenza pandemic are characterized by the worldwide spread of novel influenza strains for which most of the population lacks substantial immunity [1, 2] . Pandemic viruses typically cause heightened morbidity and mortality [1] . The continued circulation of highly pathogenic avian influenza (HPAI) viruses H5N1 has resulted in occasional coincident infections among humans. Since late 2003, when widespread H5N1 virus poultry outbreaks were reported in multiple countries in Asia, there have been 467 laboratory confirmed human cases in ten countries reported to the World Health Organization as of December 2009 with a mortality rate of about 60% [3, 4] . Global public health concerns surrounding H5N1 viruses include not only individual transmission events between infected poultry and individual humans, but also their pandemic potential, should these viruses acquire genetic changes that result in sustained human-to-human transmission. To date, several case clusters of H5N1 infections have been reported [5] and limited epidemiologic information has suggested person-to-person transmission of H5N1 in a few instances, usually involving family members. Of additional concern to both human and animal health, is the extensive geographic spread of HPAI H5N1 viruses in recent years and their isolation from multiple species of wild birds and mammals [6] [7] [8] [9] . Despite the recent emergence of the 2009 H1N1 pandemic [10] , the pandemic threat from HPAI H5N1 viruses has not diminished [11] .