SUMMARYPurpose: CO 2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO 2 can be used to suppress seizures in epilepsy patients. The effect of CO 2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans. Methods: In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. Five percent CO 2 was applied for 5 min, 3 min before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drugresistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO 2 in medical carbogen shortly after electrographic seizure onset.Results: In rats, 5% CO 2 strongly suppressed cortical afterdischarges, by approximately 75%, whereas responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO 2 from 37 to 44-45 mm Hg (corresponding to inhalation of 5% CO 2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicucullineinduced epileptiform spikes by approximately 25%. In a pilot trial carried out in seven patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO 2 was started after seizure generalization. Conclusions: Five percent CO 2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO 2 can be used for acute treatment to suppress seizures in epilepsy patients.