On September 14, 1999, the National Veterinary Services Laboratories (NVSL) of the U.S. Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS) isolated a virus from nerve and other tissues of flamingos and pheasants from the Bronx Zoo and crows from the New York City area.

Samples of the isolated virus were sent to the U.S. Department of Health and Human Services Center for Disease Control and Prevention (CDC) for identification. On September 27, CDC officials announced that the isolated virus was very similar to that of the West Nile Virus, previously unseen in the Western Hemisphere. CDC later confirmed the virus as West Nile and connected it to an encephalitis outbreak that killed 7 people and infected at least 55 others in the New York City area earlier that same year.

West Nile Virus (WNV) was first isolated in Uganda in 1937 and has been known to cause asymptomatic infections and fevers in humans in Africa, West Asia, and the Middle East. In 1957, the virus was blamed for the deaths of several elderly patients in Israel. In 1960, it was observed in horses in Egypt and France. Human and animal infections were not documented in the Western Hemisphere until the New York City outbreak in 1999. During 1999 and 2000, 83 humans (with 9 deaths) and 85 horses were diagnosed with encephalitis caused by West Nile Virus. The infections were located in numerous states along the east coast.

In 2001, human infection with WNV occurred in 10 states with 66 cases and 9 deaths. In 2002, WNV activity has spread to most eastern and mid-western states, with several hundred cases reported and many deaths. According to the National Center for Infectious Diseases, most of the WNV infections have occurred in Louisiana, Texas and Mississippi