Surveillance for H5 and H7 subtypes of avian influenza virus (AIV) in the live-bird markets (LBMs) of the northeastern United States has been in effect since 1986 when the markets were first recognized as a potential reservoir for AIV. Long-term maintenance of AIV in the LBM system has been documented. However, little is known about the influence of successive cycles of replication in unnatural avian hosts (gallinaceous birds) on the genetics of the virus, especially in the region of the hemagglutinin (HA) gene that can influence pathogenicity. Isolation of low-pathogenicity H5 AIVs from the LBMs has been sporadic; however, in 1994 a low-pathogenicity H7N2 virus was isolated that has persisted in the LBMs for more than 7 yr. Efforts to eliminate the H7 virus from the markets have been unsuccessful. During the 7-yr period, several molecular changes have occurred at the hemagglutinin cleavage site of the H7 virus. These changes include substitutions of proline for threonine and lysine for asparagine, respectively, at the −2 and −5 positions of the HA1 protein. In addition, there has been a 24 nucleotide base-pair deletion in the receptor binding region of the HA1. The accumulation of an additional basic amino acid at the cleavage site is a cause for concern to regulatory authorities, and, therefore, efforts to eliminate the virus from the LBM system have been intensified.