To investigate whether a physiological change in the orthostatic condition is associated with a deterioration of cerebrovascular and metabolic homeostasis in patients with neurocardiovascular compromises, we examined 10 patients with unilateral carotid artery occlusive disease (CVD), 6 CVD patients with coronary artery disease (CVDC), and 10 healthy subjects scanned twice under supine and sitting conditions by positron emission tomography (PET). Repeated measures analysis of variance showed significant reductions in regional cerebral blood flow (rCBF) and cerebral oxygen metabolism (rCMRO2) and tendency of increase in oxygen extraction fraction (OEF) in the affected-side parietal cortex during assuming of upright posture in the CVDC group, and there was a significant OEF increase to maintain rCMRO2 constant during sitting in the CVD counterpart. In this ischemic region, there were negative correlations between changes in OEF and rCBF in the CVD (P < 0.05) and CVDC groups (P < 0.01). Postural reductions in rCBF and CMRO2 in the parietal region were significantly greater in the CVDC group than those in the CVD group. While rCBF remained constant with mean arterial blood pressure (MABP) in healthy subjects, an rCBF reduction was found in the affected parietal cortex in proportion to the upright posture-induced MABP decrease in the CVDC group. These results indicate that patients suffering from both cerebral and coronary artery diseases may be at greater risk of deterioration of local perfusion pressure and metabolic regulation in the hemodynamically susceptible brain region during upright posture.