Toluene is one of the most widely used solvents. Electrophysiological studies indicated that this solvent directly affects various ligand gated ion channels including NMDA, GABA(A), nicotinic and glycine receptors. The effect of toluene on seizures induced by chemoconvulsants acting on these receptors was compared. Mice were pretreated with toluene (100-1000 mg/kg, i.p.) or corn oil followed by a timed intravenous infusion of NMDA, bicuculline, picrotoxin, nicotine or strychnine to induce seizures. Toluene increased seizure thresholds and lethal doses induced by nicotine, NMDA, picrotoxin and bicuculline, but not strychnine in the used doses. The relative susceptibility to anticonvulsant effect of toluene was in the order: nicotine>> NMDA>> bicuculline>> picrotoxin>> strychnine. These findings support a unique anticonvulsant profile of toluene and suggest that nicotinic and NMDA receptors may be more sensitive than GABA(A) and glycine receptors to toluene exposure in seizure-related neural circuits.