The clinical manifestations and prognosis of peripheral vascular disease (PVD) depend upon the severity of limb hypoxia. Transcutaneous oxygen tension (Ptco2) is related to tissue oxygenation, but limb Ptco2 varies with changes in systemic as well as peripheral oxygen delivery (Do2). Previously we have found that simultaneous assessment of limb and chest Ptco2 yields a ratio, or regional perfusion index (RPI), that is independent of systemic Do2 and accurately reflects the adequacy of limb perfusion. Analysis of segmental limb Ptco2, RPI, and position-induced RPI changes was performed in 24 control limbs and 14 limbs with intermittent claudication (IC), 8 limbs with rest pain (RP), and 7 limbs with gangrene (G). Control limbs had high RPI values that varied little with position. The IC group had modestly decreased RPIs in the supine position, but extremity RPIs decreased markedly during leg elevation. Patients with RP had ischemia while supine, but the RPI improved to nearly normal upon standing. Feet with G were hypoxic even in the standing position. Segmental RPI decreases correlated with the presence of significant arterial lesions. This correlation was unaffected by diabetes. Analysis of regional transcutaneous oximetry allows classification of PVD by quantitative criteria based upon the adequacy of limb perfusion under functional conditions. RPI is characteristically high in normal persons and low in persons with G. Limbs with marginally compensated perfusion may have nearly normal RPI values under some conditions, but typical ischemic changes are elicited by positional change and exercise. The ease of such provocation of RPI decreases constitutes an index of the severity of disease. Such quantitative assessments of limb hypoxia can form the basis for a physiologic approach to arterial reconstruction.