Iomazenil is a specific ligand for central-type benzodiazepine receptors (BZR). In order to determine the clinical significance of the findings of 123I-iomazenil single photon emission tomography (SPET) in cerebrovascular disease (CVD), we compared the cerebral uptake of 123I-iomazenil with oxygen metabolism measured by positron emission tomography (PET). Depending on the severity of the haemodynamic and/or metabolic impairment based on our institutional criteria [a reduction of < 30.6 ml 100g-1 min-1 in cerebral blood flow (CBF) and an increase of > 0.52 in the oxygen extraction fraction (OEF)], the cortical areas were classified into four groups as follows: Group I, normal CBF and OEF; Group II, normal CBF and increased OEF; Group III, reduced CBF and normal OEF; Group IV, reduced CBF and increased OEF. Seven patients (mean age 65 +/- 7 years) with CVD underwent both PET and 123I-iomazenil SPET within 8 days. The ratios of the mean counts in 14 regions of interest in the cerebral cortices to those in the cerebellar cortices (R/C ratios) were compared with the cerebral metabolic rate of oxygen (CMRO2). The R/C ratios of Group IV were lower than those of Group I (P < 0.005). The R/C ratios correlated with CMRO2 in Group III (r = 0.577, P < 0.01) and in Group IV (r = 0.707, P < 0.005), but not in Groups I or II. These results suggests that reduced uptake in 123I-iomazenil SPET reflects oxidative hypometabolism causing neuronal damage in haemodynamically and metabolically impaired areas in patients with CVD. This information may be valuable when deciding therapeutic approaches.