Prostaglandin E1 (PGE1) may relieve rest pain and heal ulcers in critical limb ischemia, but its mechanism of action is still incompletely understood. To investigate the effects of PGE1 treatment on endothelial function evaluated as brachial artery flow-mediated vasodilation (FMV) and on soluble adhesion molecule plasma levels (vascular adhesion molecule-1 [sVCAM-1] and intercellular adhesion molecule-1 [sICAM-1]), 12 patients with critical limb ischemia were treated with daily PGE IV infusion (alprostadil 60 microg) for 2 weeks. FMV and plasma sICAM-1 and sVCAM-1 concentrations were determined at baseline, after the first infusion, and after 1 and 2 weeks. Compared with 30 healthy control subjects, patients had higher baseline sVCAM-1 (2.402 +/- 296 ng/ml vs 972 +/- 117 ng/ml) and sICAM-1 levels (464 +/- 51 ng/ml vs 206 +/- 37 ng/ml, both p < 0.05) and lower FMV (1.0 +/- 1.1% vs 5.6 +/- 1.6%, p < 0.05). sICAM-1 concentration progressively decreased with treatment (from 464 +/- 51 ng/ml to 326 +/- 56 ng/ml, 288 +/- 42 ng/ml, and 279 +/- 44 ng/ml after the first dose and, respectively, after 1 and 2 weeks; all p < 0.05). sVCAM-1 showed a reduction after 2 weeks (from 2.402 +/- 296 ng/ml to 1.916 +/- 176 ng/ml; p < 0.05). FMV improved after 1 and 2 weeks (from 1.0 +/- 1.1% to 3.1 +/- 0.6% and 5.2 +/- 2.1%, both p < 0.05). In conclusion, treatment with PGE1 determines a significant improvement in endothelial function in patients with critical limb ischemia.