The neurotrophin-4 and glial cell line-derived neurotrophic factor levels were measured in cerebrospinal fluid from 61 patients with bacterial meningitis, viral meningitis, or encephalitis, and other diseases by means of two-site enzyme-linked immunoassay. Elevated cerebrospinal fluid levels of neurotrophin-4 were demonstrated in four of the 11 patients with bacterial meningitis, and seven of the 23 patients with viral meningitis or encephalitis. None of the other patients demonstrated elevation of the neurotrophin-4 level in cerebrospinal fluid. The neurotrophin-4 levels in cerebrospinal fluid were correlated with the numbers of total and mononuclear cells in patients with viral meningitis/encephalitis. In patients with bacterial meningitis, three of the four patients with elevated neurotrophin-4 levels exhibited persistent abnormalities on computed tomography, and one revealed transient subdural effusion. On the other hand, none of the seven patients without neurotrophin-4 elevation had persistent computed tomography abnormalities, and five patients demonstrated transient computed tomography abnormalities. The glial cell line-derived neurotrophic factor levels were below the detection limit, or only slightly higher than the detection limit, in the patients with or without central nervous system infections. Although the precise roles of neurotrophin-4 and glial cell line-derived neurotrophic factor in central nervous system infections remain to be determined, neurotrophin-4 might play a neuroprotective or immunomodulatory role in central nervous system infections.