The present study was performed in order to compare: 1) the differences between oral and intravenous barbiturate on interictal epileptiform activity (sharp-waves and spikes) in the EEG, and 2) interictal epileptiform activity in the sphenoidal electrode compared to the temporal and zygomatic electrodes (an electrode placed at the cutaneous entry of the sphenoidal electrode) during intravenous barbiturate administration in patients with epilepsy. Two procedures were performed: 1) an oral pentobarbital sleep induction with 10-20 electrode placement including a zygomatic electrode, and 2) an intravenous thiopental sleep induction with the same electrode placement including a sphenoidal electrode. Thirty eight patients with complex partial seizures were included. During the oral pentobarbital procedure 34 of 38 (90%) patients showed interictal epileptiform activity compared with 22 of 38 (55%) patients during the intravenous thiopental procedure (p < 0.005). A interictal epileptiform focus was observed in 33 (87%) patients in the oral procedure and in 19 (50%) patients in the intravenous procedure (p < 0.01). Interictal epileptiform activity recorded in the sphenoidal electrode was also recorded in the zygomatic electrode. Except from two patients a good correlation was observed between the zygomatic electrodes and the F7/F8 electrodes. We conclude that administration of intravenous thiopental offers no advantage compared to the administration of oral pentobarbital as an activating procedure, and for standard interictal EEG recordings with sleep activation procedures, suitable places scalp electrodes including a zygomatic electrode with the use of oral pentobarbital may be sufficient.