Results of experiments evaluating the efficacy of three immunization strategies for the prevention of West Nile virus (WNV) encephalitis are reported. Immunization strategies evaluated included a killed virus veterinary vaccine, a live attenuated chimeric virus vaccine candidate, and passive immunization with WNV-immune serum; all were tested by using a hamster model of the disease. Each product protected the animals from clinical illness and death when challenged with a hamster-virulent wild-type WNV strain 1 month after initial immunization. The live attenuated chimeric virus vaccine candidate induced the highest humoral antibody responses, as measured by hemagglutination inhibition, complement fixation, and plaque reduction neutralization tests. Although the duration of protective immunity was not determined in this study, our preliminary results and the cumulative experience of other virus vaccines suggest that the live attenuated chimeric virus provides the longest lasting immunity.