We have used laser Doppler flowmetry (LDF) for real-time monitoring of regional cerebral blood flow (rCBF) during epileptic seizures recorded intracranially with subdural electrodes. The method was employed in six patients with medically intractable epilepsy undergoing preoperative evaluation for epilepsy surgery. rCBF was measured during 24-h video/EEG monitoring of seizures. Eleven seizures were recorded with simultaneous LDF and EEG by a combined subdural EEG electrode and laser Doppler probe. All seizures recorded on EEG were accompanied by distinct changes in rCBF. There was either an increase in blood flow up to 100% or a decrease by 30% from the basal levels. The ictal blood flow changes were similar comparing seizures within one patient, whereas striking differences were found between patients. The rCBF was also studied interictally. Different blood flow signal patterns were found correlating to the wakefulness of the patient. The LDF technique, combined with continuous EEG recording, appears to be a powerful tool for studying regional transient rCBF changes in association with focal epileptic seizure activity.