Avian influenza viruses replicate to high titers in the cells lining the intestinal tract of birds; however, human strains do not. A series of reassortant viruses with all six internal genes from an avian strain and one or both genes for the surface antigens from a human strain failed to transit and infect the intestinal tracts of ducks. However, these reassortants did replicate in the bursa of ducks after rectal inoculation. These studies provide the first evidence that the hemagglutinin and neuraminidase are critical for the enterotropism of avian viruses but are not essential for replication in other avian tissues.