A double-blind, crossover study was designed to evaluate the effect of L-carnitine on the reactive hyperemia in patients with peripheral vascular disease. After drug washout, 18 patients were randomly assigned to receive placebo or L-carnitine, 3 g IV as a bolus, followed by continuous intravenous infusion of 2 mg/kg/min for thirty minutes. Blood flow in the affected limb was measured by impedance plethysmography, under resting conditions and every two minutes for ten minutes after a five-minute ischemia induced in the affected limb. As compared with placebo, L-carnitine did not modify blood flow at rest. On the contrary, the hyperemic response with carnitine was higher than that observed with placebo. A significant increase in blood flow was found two, four, and six minutes after the release of ischemia with placebo, whereas the blood perfusion to the affected limb rose significantly at all times of recording after carnitine administration. Moreover, the values of the blood flow at two and ten minutes with carnitine were significantly higher than those recorded after placebo at the same times of recording. After the release of ischemia, the mean maximum value of blood flow observed after carnitine was 3.1 +/- 1.4 mL/min/100 mL, a value significantly higher than that recorded after placebo, which was 2.7 +/- 1.3 mL/min/100 mL (p less than 0.05). In conclusion, this study demonstrates that L-carnitine, although not affecting blood flow and ankle/arm systolic blood pressure ratio under resting conditions, improves the functional circulatory reserve in patients with peripheral vascular disease.