WNV encephalitis in horses, previously reported in Africa, Asia, and Europe, occurred for the first time in the Western Hemisphere in 1999. The causative agent, WNV, is a flavivirus maintained in nature by a bird-mosquito cycle. The disease in horses is manifested primarily by ataxia of variable severity. Outbreaks of encephalitis may have a case fatality rate in excess of 40%, although this virus infection is inapparent in some horses. Early evidence indicates that WNV has overwintered in the northeastern United States and poses a threat for future disease occurrences in horses. No vaccine is available to protect against WNV infection in horses; disease control is predicated on mosquito abatement.