Peripheral arterial occlusive disease (PAOD) is characterized by atherosclerotic lesions in large vessels and disturbances on the microcirculatory level. In the local regulation of vascular tone and microvascular perfusion, vascular endothelium plays a key role. For many years prostaglandin E1 (PGE1) has been used for the treatment of PAOD. Because PGE1 has only moderate effects on blood flow other mechanisms may be relevant for the therapeutical efficacy. The aim of our pilot study was to evaluate endothelial function in patients with PAOD and to investigate the impact of PGE1 on endothelial-dependent vasodilation in peripheral vessels In 8 controls and in 8 patients with PAOD stage II, endothelial-dependent vascular responses of the femoral vessels to increasing doses of acetylcholine (30,60,90 μg/min) were determined by Doppler flow velocity measurements in the common femoral artery. Furthermore, vascular reactivity was evaluated before and immediately after intravenous infusion of 30 μg PGE1/30 min in patients. Endothelial-dependent vasodilation was significantly reduced in patients with PAOD compared to control subjects. Infusion of PGE1 neither increased blood flow in the common femoral artery nor endothelium-dependent vasodilation of peripheral resistance vessels as indicated by unchanged reaction to acetylcholine. In conclusion, endothelial function is impaired in patients with PAOD. Administration of PGE1 did not increase femoral artery blood flow or improve endothelial-dependent reactivity of peripheral resistance vessels in patients with PAOD. Therefore, beneficial effects of PGE1 in peripheral vascular disease cannot be attributed to an increase in blood supply or an improvement of endothelial-dependent vasodilation.