This study was performed on 35 albino rats prepared for acut and 18 for chronic experiments. The midbrain reticular formation was electrolytically destroyed on both sides in 24 animals, and in 11 on one side. The interruption of the reticular activating system was checked by strong nociceptive and electrical stimulation below the lesioned area. In acute preparations pentobarbital was given by intravenous injection in increasing doses, and in chronic experiments by intraperitoneal injections. The barbiturate always augmented synchronization of the electrocorticogram but induced an early depression of the electrical activity in rats with bilateral extensive lesions. After barbiturate administration the electro-corticogram of both hemispheres tended to became more isochronized. Pentobarbital seems to depress the activating systems in small doses, thus liberating the synchronizing systems, whereas larger doses block also the latter. Only very large doses depress the cortical activity.