Clinical evaluation of 123I-iomazenil, a new imaging agent for central-type benzodiazepine receptors with SPECT, was performed in patients with ischemic cerebrovascular disease. We investigated 15 patients with angiographically-proven severe occlusive lesions (occlusion or > 70% stenosis) in the unilateral carotid system. 123I-iomazenil SPECT images were compared with cerebral blood flow (CBF) images and the cerebral perfusion reserve, which were measured using the "split dose 123I-IMP SPECT method" before and after the intravenous injection of 1 g of acetazolamide. For the detection of ischemic lesions, CBF images were superior to 123I-iomazenil images based on visual analysis. Regarding the count ratio of the affected MCA territory to the non-affected (L/N), 123I-IMP was lower than 123I-iomazenil in most of the cases. In five patients showing "crossed cerebellar diaschisis" by 123I-IMP, asymmetry of the cerebellar accumulation was observed in only one patient with 123I-iomazenil, which was less prominent than with 123I-IMP. There was no significant correlation between the L/N ratio with 123I-iomazenil and the cerebral perfusion reserve in the affected MCA territory. However, in some cases showing a decreased L/N ratio (< 90%) with 123I-iomazenil, a decreased CBF with normal perfusion reserve and cerebral hemi-atrophy were observed with 123I-IMP and MRI, which suggested the influence of neuronal loss due to chronic ischemia. These results indicate that 123I-iomazenil SPECT, which provides new information regarding neuronal loss due to ischemic damage to the brain, is useful for the evaluation of ischemic cerebrovascular disease.