The historic and dreaded synonym used to describe the disease caused by highly pathogenic (HP) avian influenza virus is fowl plague. Less pathogenic strains of avian influenza have caused problems in many US turkey flocks and live poultry markets since the 1960's, while few commercial chicken flocks were involved. However in 1983, a virus originally characterized as relatively nonpathogenic began to produce a fowl-plague-like disease with high death losses in Pennsylvania. Control and eradication of this 1983 outbreak cost over $63 million in Federal funds and an additional $350 million in increased consumer costs. As of 1998, viruses related to those involved in the 1983 outbreak continue to circulate in North America and to pose a threat to the US Poultry industry. The recent highly publicized outbreak of H5N1 avian influenza (AI) in chickens and people in Hong Kong illustrates the potential public health concerns that may surface as a result of AI infections. SEPRL Research efforts on avian influenza are directed toward understanding why and how mild viruses become highly pathogenic, developing better diagnostic tests and improved vaccines, and elucidating the molecular and pathological basis for virulence. The molecular research includes identification and characterization of genes using the PCR procedure, sequencing of the entire virus genome of representative isolates, molecular modeling and phylogenetic analyses of field strains. The basic genetic structure is related to the behavior of the virus in living hosts with the goal of developing ways to predict pathogenicity potential of influenza viruses.