Cerebrospinal fluids (CSFs) and sera from 20 patients with echovirus 30 (E 30) meningitis, 4 patients with enterovirus 71 (EV 71) meningitis, and 5 patients with acute aseptic meningitis (AM) of unknown etiology were investigated at the acute and the convalescent phases of the disease to elucidate the roles of neutralizing antibody (NT) and interferon-a (IFN-a) in the central nervous system (CNS) in cases of AM in humans. Viruses were isolated from the CSFs at the acute phase of AM, but not at the convalescent phase. There was a fourfold or greater rise in NT titer between paired sera to E 30 or EV 71 but only a slight rise between paired CSFs. IFN-a was detected in the CSFs ranging from < 10 to 25.5 IU/ml but not in the sera, and the IFN-a level in the CSF was significantly higher in the acute phase than in the convalescent phase. These results suggest that in cases of acute enteroviral infections in the CNS, NT plays only a small role in the recovery from AM, and IFN-a plays a direct or indirect role in curbing the local spread of the virus and eliminating the virus from the CNS at the acute phase of AM.