Although passive administration of immune human γ-globulin after WNV infection improved survival in mice 4,5 , it may be limited by its low-titer neutralizing activity, variability and risk of transmission of infectious agents. Only two prior studies have shown postexposure therapy of neutralizing monoclonal antibodies with flaviviruses: 6B5A-2 reduced mortality 3-4 d after infection with St. Louis encephalitis virus 6 ; and 503 reduced mortality resulting from infection with Japanese encephalitis virus 5 d 32 . Here, we show that three different neutralizing monoclonal antibodies improved survival even when administered 4 and 5 d after WNV infection. Moreover, therapy with E16 at day 5 completely cleared WNV from the brain at day 9 in 68% of mice. Thus, inhibitory WNV monoclonal antibodies improve clinical and virologic outcome even after viral spread through the CNS, results that agree with studies showing that antibody can mediate viral clearance from infected neurons 33, 34 .