This report describes a new hamster model for West Nile (WN) virus encephalitis. Following intraperitoneal inoculation of a New York isolate of WN virus, hamsters had moderate viremia of 5 to 6 days in duration, followed by the development of humoral antibodies. Encephalitic symptoms began 6 days after infection; about half the animals died between the seventh and 14th days. The appearance of viral antigen in the brain and neuronal degeneration also began on the sixth day. WN virus was cultured from the brains of convalescent hamsters up to 53 days after initial infection, suggesting that persistent virus infection occurs. Hamsters offer an inexpensive model for studying the pathogenesis and treatment of WN virus encephalitis.