Effects of baclofen on the cortical electrical paroxysm were examined using slices of the guinea pig hippocampus. A very low concentration of baclofen (10(-8) M) readily suppressed spontaneous epileptiform discharges of CA3 pyramidal cells, whereas synaptic transmission between mossy fibers and CA3 pyramidal cells were not affected even by 10(-4) M of this drug. Such a strikingly selective depressant action of baclofen on the epileptiform activity raises a possibility that this drug may be effective in the treatment of epilepsy.