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Widespread outbreaks of avian influenza in domestic fowl throughout eastern Asia have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic. Simultaneous infection of humans (or swine) by avian influenza viruses in the presence of human influenza viruses could theoretically generate novel influenza viruses with pandemic potential as a result of reassortment of genome subunits between avian and mammalian influenza viruses. These hybrid viruses would have the potential to express surface antigens from avian viruses to which the human population has no preexisting immunity. This article reviews current knowledge of the routes of transmission of avian influenza A viruses to humans, places the risk of appearance of a new pandemic influenza virus in perspective, and describes the recently observed epidemiology and clinical syndromes of avian influenza in humans.