Although sphenoidal electrodes are widely used to detect epileptiform activity, there is no agreement on an optimal target to which electrodes should be aimed. The purpose of this study was to determine whether fluoroscopic guidance is a reliable method for placing electrodes directly below the foramen ovale and whether such positioning enhances their capacity to detect epileptiform activity when compared to similar electrodes placed blindly into the infratemporal fossa. We examined the surface/sphenoidal EEG recordings of 17 patients with intractable partial seizures of anterotemporal origin, after fluoroscopically placed sphenoidal electrodes (FPSE) had been inserted to lie just below the foramen ovale. A criterion for eligibility was a previous prolonged video/EEG monitoring with blindly placed sphenoidal electrodes (BPSE) that failed to detect seizures with a focal onset. No blindly placed electrode, for which there was radiographic documentation, reached the foramen ovale. Fluoroscopic guidance assured accurate targeting. FPSE detected a unilateral anterotemporal interictal focus in four patients in whom BPSE had failed to record any interictal spikes and detected bitemporal independent interictal foci in one patient in whom BPSE had identified only unilateral spikes. In nine other patients, the spike count obtained with FPSE recordings increased by > 100% when compared to that obtained with BPSE recordings. FPSE recorded seizures with an anterotemporal focal onset pattern in 10 patients in whom BPSE had recorded seizures with a regional, lateralized, or nonlocalized onset pattern. In nine of these 10 patients, this was adequate to recommend surgery and avoid invasive monitoring. Fluoroscopic guidance assures accurate targeting of the foramen ovale. When compared to BPSE, FPSE resulted in better detection of interictal and ictal epileptiform activity of mesial-basal-temporal origin.