Febrile convulsions (FC) are frequent acute neurologic disturbances of childhood. The cellular and neurochemical mechanisms causing FC are unclear. Among other mechanisms, the CNS histamine (HA) has been suggested to participate in seizure control and thermoregulation. We evaluated the possible role of HA in regulation of FC by measuring HA and tele-methylhistamine (t-MH) concentrations in the cerebrospinal fluid (CSF) of children with FC. The study group consisted of 35 children treated for acute FC in the hospital. The control groups consisted of (a) feverish children without seizures (n = 23), (b) convulsive children without fever (n = 7), and (c) children with neither fever nor convulsions (n = 21). HA was assayed by high-performance liquid chromatography (HPLC) with fluorescence detection, and t-MH was measured by gas chromatography-mass spectrometry. CSF HA concentration in the group of febrile children without seizures was significantly higher (0.69 +/- 0.16 pmol/ml, mean +/- SE) than in children with FC (0.36 +/- 0.07 pmol/ml, p < 0.05, analysis of variance, ANOVA). HA concentration was 0.37 +/- 0.18 pmol/ml in the group of nonfebrile convulsive children and 0.36 +/- 0.08 pmol/ml in the nonfebrile nonconvulsive group. No statistical differences in t-MH were detected between groups. The increased susceptibility to seizures during fever may be connected to the lack of increase in CSF HA in the FC group. The data support the hypothesis that the central histaminergic neuron system may be involved in inhibition of seizures associated with febrile illnesses in childhood.