No study comparing epileptogenicity of sevoflurane to other volatile anesthetics has been performed. We compared the epileptogenic properties of sevoflurane to isoflurane in patients with epilepsy. In 24 mentally and/or physically disabled patients, 12 with epilepsy and 12 without epilepsy, electroencephalograms were recorded under anesthesia with 1.0 minimum alveolar anesthetic concentration (MAC), 1.5 MAC, and then 2.0 MAC sevoflurane or isoflurane under three ventilatory conditions: (A) 100% oxygen, and end-tidal CO, partial pressure (ETco(2)) = 40 mm Hg, (B) 50% oxygen, 50% nitrous oxide, ETco(2) = 40 mm Hg, and (C) 100% oxygen, ETco(2) = 20 mm Hg. Spike activity was evaluated as a spike-and-wave index (% durations of spike and wave). The spike-and-wave index increased (P < 0.05) from 1.99% +/- 0.96% during 1.0 MAC sevoflurane to 6.14% +/- 4.45% during 2.0 MAC sevoflurane in (A) in the epilepsy group, while no spike activity was observed in the nonepilepsy group. Only a few spikes were observed under isoflurane anesthesia, 0.04% +/- 0.04% in (A), with no spikes in (B) and (C). Supplementation with 50% nitrous oxide or hyperventilation (P < 0.05) suppressed the occurrence of spikes. Sevoflurane has a stronger epileptogenic property than isoflurane, but nitrous oxide or hyperventilation counteracts this specific epileptogenic property.