Presently available noninvasive methods correctly localize epileptogenic regions in only approximately 50% of patients with frontal lobe epilepsy (FLE). Earlier studies have shown that temporal lobe epileptogenic regions may be identified readily by positron emission tomography (PET) measurements of regional benzodiazepine (BZD) receptor binding. We tested the specific applicability of this method in patients with FLE. Six patients with frontal partial seizures and 7 healthy men were investigated with PET and the BZD receptor ligand [11C]flumazenil. All patients had magnetic resonance (MR) brain scans. The independent assessment of seizure-onset region was based on seizure semiology, intra- and extracranial EEG and, in 4 cases, also on [18F]fluorodeoxyglucose (FDG)-PET. The epileptic focus/seizure-generating region was correctly identified by [11C]flumazenil PET in all patients. This region was characterized by a significant reduction in BZD receptor density. The area with reduced BZD receptor density was better delimited than the corresponding hypometabolic region, which was observed in 50% of patients investigated with [18F]FDG-PET. MRI was normal in 5 patients. Visualization of BZD receptors with [11C]flumazenil PET appears to be a promising approach for noninvasive identification of frontal lobe epileptogenic regions.