Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of 123I-IMZ (167 MBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.