Neuron-specific enolase (NSE) and S-100 protein (S-100) levels in cerebrospinal fluid (CSF) were determined in 129 patients with various neurological diseases. The chronological changes of these nervous system-specific proteins in CSF were also examined in 3 patients with acute disorders. NSE and S-100 levels were elevated in many cases with acute conditions. These specific proteins did not increase simultaneously but independently. These results suggested that NSE and S-100 in CSF would be useful markers for damage of the nervous system and that measurement of both NSE and S-100 might positively indicate whether the damage was neuronal, glial or mixed in origin. Moreover, from the serial determination of these substances, they would be better markers than cell counts and total protein in CSF for the active injury for the nervous tissues.