Avian influenza is endemic in wild birds in North America, and the virus routinely has been transmitted from this reservoir to poultry. Influenza, once introduced into poultry, can become endemic within the poultry population. It may be successfully eradicated by human intervention, or the virus may fail to successfully spread on its own. In the last 5 yr, influenza virus has been isolated from poultry in the United States on numerous occasions, and, with the use of molecular epidemiology, the relationships of these different viruses can be determined. There are 15 different hemagglutinin subtypes of avian influenza viruses, but infections with virus of H5 and H7 subtypes are of the most concern because of the potential for these viruses to mutate to the highly pathogenic form of the virus. Most of the influenza isolations in the United States have been associated with the live-bird markets (LBMs) in the Northeast. This has included primarily H7N2 influenza viruses, but also H7N3, H5N2, and other subtypes. Most of the H7N2 viruses were part of a single lineage that was first observed in 1994, but new introductions of H7N2 and H7N3 were also observed. The predominant H7N2 LBM lineage of virus spread to large commercial poultry operations on at least three occasions since 1997, with the largest outbreak occurring in Virginia in 2002. The H5N2 viruses in the LBMs included viruses from domestic ducks, gamebirds, and environmental samples. Some H5N2 viruses isolated in different years and in different locations had a high degree of sequence relatedness, although the reservoir source, if it is endemic, has not been identified. Finally, an H1N2 virus, associated with a drop in egg production, was isolated from turkeys in Missouri in 1999. This virus was a complex reassortant with swine, human, and avian influenza genes that was similar to recent swine isolates from the Midwest. Additional serologic evidence suggests that flocks in other states were infected with a H1N2 virus.