Vaccination against highly pathogenic (HP) subtypes of avian influenza (AI) virus in poultry has been prohibited in the United States. Recently, policy has been changed to potentially allow use of inactivated vaccines in emergency programs to control HP H5 and H7 AI. Vaccination with inactivated virus against non-highly pathogenic AI viruses has been allowed in the U.S. turkey industry since 1979 (1) but requires expensive handling of individual birds for parenteral inoculation. Oral immunization would provide a less expensive method to protect commercial poultry from AI. Prime candidates for oral vaccines are waterfowl-origin (WFO) isolates, which have a tropism for the alimentary tract. One WFO isolate, A/mallard/Ohio/556/1987 (H5N9) (MOh87), was characterized by determining the complete nucleotide sequence of its hemagglutinin (HA) gene. The HA protein of this isolate possessed a deduced amino acid sequence nearly identical to the consensus amino acid sequence for all published H5 genes, indicating that it has potential as a broadly effective vaccine. Experimental results demonstrated measurable serum antibody responses to orally delivered live and inactivated preparations of MOh87. Oral vaccination also protected chickens from diverse, lethal H5 AI virus challenge strains and blocked cloacal shedding of challenge virus.