Objectives Elevated levels of soluble (s) vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1, pointing to activation of cells involved in vascular inflammation, have been previously reported in peripheral arterial obstructive disease (PAOD). We tested the hypothesis that intravenous prostaglandin E₁ (PGE₁) treatment, which produces clinical benefits in this condition, might decrease such levels. Methods Ten subjects (age range 58 ± 10 years, 6 male, 4 female) with characterized Fontaine stage IIa to IV PAOD (ankle/arm pressure index <0.96) were entered into a treatment protocol with twice daily intravenous infusions of PGE₁ (alprostadil) at 120 μg per day, repeated for 10 consecutive days. Preinfusion and postinfusion plasma samples were stored for blind enzyme immunoassays of soluble adhesion molecules and the fibrinolytic marker tissue plasminogen activator, type-1 plasminogen-activator inhibitor, and D -dimer. Results Estimates of severity of pain at rest, consumption of analgesics, magnitude of trophic lesions, remission to lower Fontaine stages, and favorable changes in the venoarteriolar reflex documented significant beneficial effects of the treatment. Significant (P <.01) pretreatment and posttreatment reductions of in all soluble markers explored were found. Particularly, sVCAM-1 exhibited a significant decrease after each infusion, which was sustained at the last day of treatment (from 854 ± 214 ng/mL to 775 ± 215 ng/mL across the first infusion, from 773 ± 146 ng/mL to 680 ± 110 ng/mL across the last infusion). Conclusion Thus a global decrease of vascular cell activation appears to occur as a result of PGE₁ administration and may contribute to the observed clinical benefits in PAOD. (Am Heart J 2001;142:733-9.)