Over the past five years, West Nile (WN) virus has emerged as an important public health concern in the United States. Recent studies from experimental models of WN virus infection have increased our understanding of its pathogenesis and immunity. These include the demonstration that the gene encoding 2'-5'oligoadenylate synthetase is responsible for murine susceptibility to WN virus, the elucidation of the contributions of B, CD8(+) and gamma T cells in the control of murine WN virus infection, and the use of active immunization with envelope protein and passive transfer of immunoglobulin for immunotherapy. These efforts will facilitate the development of effective vaccines and therapies to combat WN virus.