Platelet-activating factor acetylhydrolase was analyzed in cerebrospinal fluid samples taken from children with a variety of neurological conditions (85 patients; mean age, 3.8 years) to determine it is involved in the defense mechanism against the toxic effect of inflammatory mediators in the central nervous system. A significant increase in cerebrospinal fluid activity was seen in the patients with meningitis and acute febrile illness in comparison with the control subjects. The activity was also significantly higher in the patients with meningitis than in the patients with inflammatory neurological diseases. In addition, the biochemical profile of cerebrospinal fluid platelet-activating factor acetylhydrolase was different from other known acetylhydrolases. These findings suggest that cerebrospinal fluid platelet-activating factor acetylhydrolase activity may be a sensitive marker of the host response to central nervous system infections.