Methods: We examined interictal 123 I-IMZ SPECT in patients with mesial temporal lobe epilepsy (MTLE; n = 19) with hippocampal sclerosis and neocortical epilepsy with focal cortical dysplasia (NE-CD; n = 18), and compared those with magnetic resonance imaging (MRI) and 123 I-IMP SPECT (for regional cerebral blood flow). We also investigated in vitro autoradiography with 123 I-IMZ at various time courses in the intraamygdala kainate, amygdala kindling, and in-utero irradiation models.Results: In MTLE patients, the epileptogenic hippocampus often showed decreases in both 123 I-IMZ and 123 I-IMP SPECT. Consistent with those, marked reduction of 125 I-IMZ binding was observed in hippocampal CA1-3 regions of the kainate model, which clearly paralleled pyramidal neuronal loss. In contrast, 125 I-IMZ binding was increased in the dentate gyrus at 1 month but returned to the normal level at 3-6 months, when frequent spontaneous seizures appeared. The amygdala-kindling model demonstrated similar increases in 125 I-IMZ binding in the dentate gyrus without any changes in other brain regions. In NE-CD patients, the epileptogenic foci showed decreased 123 I-IMZ binding with relatively normal 123 I-IMP SPECT. 125 I-IMZ binding also was decreased in the cerebral cortex, hippocampus (areas CA1, 2, and 4), and caudate/putamen of the in-utero irradiation model.Conclusions: These results indicate that central-type BZRs neuroimaging is useful for detection of epileptogenic foci, but their alterations differ between epilepsy subtypes and time-courses.