The effect of histamine (Hi) on the evoked potentials recorded from the nucleus ventralis posteromedialis thalami (VPM) and the midbrain reticular formation (RF) was studied in unanesthetized rabbits. Under pentobarbital anesthesia, the recording electrodes were implanted stereotaxically into the VPM and RF, and stimulating electrodes were inserted into the tooth pulp of both incisors of rabbits. To maintain a high electrical resistance between the stimulating electrodes, attention was paid to selecting a suitable material for protecting the soldering point. When the tooth pulp was stimulated by the repetition of square wave pulses either ipsilaterally or contralaterally, similar evoked potentials were recorded at the VPM and RF. The potentials were biphasic consisting of an initial negative deflection followed by a positive deflection. Contralateral stimulation induced larger amplitude waves with shorter latencies than those of ispilateral stimulation. Intraventricular administration of Hi decreased the amplitudes of evoked potentials in a dose-dependent fashion. The effect of 200 μg of Hi corresponds to that produced by intravenous administration of 2 mg/kg of morphine. When the same dose of Hi was given together with 20 μg of pyrilamine, the depression of the potentials was eliminated remarkably, but visible alteration was not brought about by simultaneous administration of cimetidine.