The relative magnitude of endothelial versus non-endothelial vasodilatation in the skin of limbs of patients with peripheral arterial occlusive disease (PAOD) is not known. We therefore investigated the effects of iontophoretically administered sodium nitroprusside (SNP) and acetylcholine (Ach) on the skin microvascular blood flow measured by laser-Doppler fluxmetry. METHODS Blood flow changes in the skin was measured on the dorsal side of the foot in three different groups: (i). 11 patients (mean age 73 years) with PAOD, with a mean ankle-brachial index of 0.46, (ii). eight age-matched elderly healthy volunteers (mean age 73 years) and (iii). young healthy group (n=15; mean age 34 years). For drug administration with iontophoretic technique we used a Periont Micropharmacology System. RESULTS In patients with PAOD, Ach produced a vasodilatation, which was directly correlated to the strength of iontophoretic stimulation. The difference between the patients and the elderly healthy group was significant after the highest stimulation (160 s, P<0.05). The same pattern was found during stimulation with SNP. In comparison with the young healthy group there was a statistically significant difference (P<0.001) with a slower and less pronounced response in patients with PAOD. CONCLUSIONS In patients with PAOD it is possible to achieve local vasodilatation from a baseline level by delivering Ach or SNP through the skin. The two vasodilators, acting by different mechanisms, produced the same vasodilatation response, suggesting that the impaired vasodilatation capacity in patients with peripheral arterial disease may not emanate primarily from local endothelial dysfunction in the skin microcirculation.