This study reports the detection of autoantibodies to myelin basic protein (MBP) and neurofilament proteins (NFP) in serum and cerebrospinal fluid (CSF) of Japanese encephalitis patients. The diagnosis of Japanese encephalitis was confirmed in 72 patients by the presence of virus specific antibodies to JEV in the CSF (28/72), viral antigen in the CSF (19/72) and simultaneous presence of both antigen and JEV antibodies in the CSF in 25/72 patients. Autoantibodies to either purified NFP (10) or MBP (8) or both (17) were detected in the CSF of 35 patients by ELISA in contrast with the control CSF samples. Amongst them 20 had similar antibodies in the serum as well. Correlation of immunological findings with the clinical outcome revealed that the presence of autoantibodies in the CSF especially to NFP was associated with a fatal outcome (P < 0.05).