PURPOSE: CO₂ has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO₂ can be used to suppress seizures in epilepsy patients. The effect of CO₂ 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 CO₂ 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 drug-resistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO₂ in medical carbogen shortly after electrographic seizure onset. RESULTS: In rats, 5% CO₂ strongly suppressed cortical afterdischarges, by approximately 75%, whereas responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO₂) from 37 to 44-45 mm Hg (corresponding to inhalation of 5% CO₂ or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced 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% CO₂ was started after seizure generalization. CONCLUSIONS: Five percent CO₂ has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO₂ can be used for acute treatment to suppress seizures in epilepsy patients.