Neuropharmacological studies were undertaken to investigate the mode of action of perimetazine. 1) Sedation, hypothermia, muscle relaxation and other signs of central depressant effects were observed after perimetazine administration in the rabbit. 2) Neuro-muscular transmission was not affected by intravnous injection of perimetazine, but was slightly facilitated by a large dose of intraarterial injection of the drug 3) Perimetazine slightly depressed spinal reflex potentials in the spinal cat and markedly reduced them in the anaesthetized cat and the decerebrate cat. 4) Permetazine reduced decerebrate rigidity in the rabbit, and decreased muscle spindle discharges in the decrebrate cat. 5) Perimetazine had no effect on the response of superior cervical ganglion but suppressed the response of the cat nictitating membrane. 6) In the rabbit, perimetazine elicited a drowsy pattern in the spontaneous EEG and inhibited the EEG arousal response induced by auditory stimulation, but failed to depress the EEG arousal response induced by electric stimulation of the mesencephalic reticular formation. These results suggest that perimetazine has central nervous system depressent effects such as sedative and muscle relaxant effects, and its mode of action is similar to that of chlorpromazine.