Eighty-five paediatric patients in Thailand with acute Japanese encephalitis (JE) were studied in 1987-99 to determine risk factors present at hospital admission which were associated with severe disease. On univariate analysis, the following factors on admission were significantly associated with the combined end-point of death or a severe neurological deficit: depressed level of consciousness, elevated concentration of cerebrospinal fluid (CSF) protein, low levels of serum and CSF IgG antibody against Japanese encephalitis virus (JEV), low level of serum IgM antibody against JEV, and a serological response consistent with primary flavivirus infection. On multivariate analysis, an initial serum anti-JEV IgM < 150 U and the absence of a prior flavivirus infection, presumably dengue, remained independent risk factors for death or a severe neurological deficit. The ability to mount an early and vigorous JEV-reactive antibody response is associated with a better outcome from acute JE. An anamnestic, anti-flavivirus, immune response induced by a prior dengue virus infection can be an important means of providing this protection.