The effects of L-propionylcarnitine on walking capacity were assessed in a group of patients with peripheral vascular disease. in 12 patients. 300mg of L-propnionylcarnitine, given intravenously as a single bolus did not affect walking capacity, while 600mg increased both initial claudication distance from the placebo value of 179±114 to 245 ± 129 m (P<0.05), and maximal walking distance from 245±124 to 349±155m (P<0.05). Once the efficacious dose of L-propionylcarnitine was assessed, its effect was compared to that of an equimolar dose of L-carnitine (500 mg i.v.) according to a double-blind, double-dummy, cross-over design. In 14 patients, both treatments improved walking capacity; however, the analysis of variance showed that the increase in maximal walking distance with L-propionylcarnitine was greater than that with L-carnitine (P < 0.05). Finally, in seven additional patients, the effects of L-propionylcarnitine and L-carnitine on the haemodynamics of the affected limb were assessed by an ultrasonic duplex system. Results indicated that both drugs did not affect the blood velocity and the blood flow rate in the ischaemic leg, thus suggesting that the beneficial effect on walking capacity was dependent on a metabolic effect. In conclusion, L-propionylcarnitine improves walking capacity in patients with peripheral vascular disease, probably acting through a metabolic mechanism. On a molar basis, this beneficial effect is greater than that observed with L-carnitine and, thus, the findings of the present study may have clinical relevance in terms of treatment cost and patient compliance. © 1992 The European Society of Cardiology.