The present experiments aimed to elucidate the mechanisms of excitatory effects of volatile anesthetics. In ddN mice, enflurane (2% in air), sevoflurane (2%) or isoflurane (1.2%) induced opisthotonus. In ddY mice, a halogenated ethane, tetrachlorodifluoroethane (CCl2FCCl2F:DF-112, 2%) induced tonic-clonic convulsion. These CNS excitatory effects were suppressed by pretreatment with an N-methyl-D-aspartate antagonist, MK-801 (0.5mg.kg-1). Halogenated volatile anesthetics (enflurane, sevoflurane, isoflurane and halothane) increased glutamate release from synaptosomes of the mouse cerebral cortex at concentrations corresponding to those used clinically. The convulsive gas, DF-112, released glutamate more potently than the anesthetics. These data suggest the involvement of enhanced glutamate release in the mechanisms of excitatory effects of halogenated volatile anesthetics.