Detection and localization of peripheral arterial disease was evaluated by intravenous injection of 201Tl at peak exercise in 22 subjects. Images of the gluteals (G), thighs (T), knees (K), and calves (C) were obtained at exercise and after a 3 hr delay, and stored in a computer, interextremity (T/T and C/C) and intraextremity (G/T, T/C, T/K) counts ratios were calculated. Normal values were defined in 11 control subjects and compared with those obtained in 11 patients with angiographically proven peripheral arterial disease. Bilateral disease was detected scintigraphically in all patients. T/T and G/T ratios correctly predicted proximal disease in nine of 12 limbs, while C/C, T/C, T/K ratios correctly predicted distal disease in 21 of 21 involved limbs. Delay images 3 hr after stress generally reverted towards the norm. Objective systematic evaluation of limb isotope uptake permits accurate detection and localization of peripheral arterial disease. Method accuracy compares favorably with physical signs and with other noninvasive methods of detection of peripheral vascular disease. Scintigraphy presents advantages which indicate great clinical potential.