BACKGROUND In advanced atherosclerosis, endothelial lesions and turbulent flow in stenotic vessels result in platelet aggregation with the liberation of vasoactive factors, including thromboxane A2 and serotonin. This study was designed to assess the combined effect of these factors on arterial dimensions at the time of limb angiography in patients with advanced peripheral vascular disease. METHODS Diameter changes of 53 segmental stenosis of large arteries were measured in digitized angiograms by a computerized objective method in response to either placebo (13 segments in 7 patients), ketanserin (23 segments in 23 patients), or ketanserin superimposed on aspirin (17 segments in 7 patients). Responses of arterial collaterals were evaluated by a coded assessment. Statistically significant vasodilatation was observed in both the stenotic and post-stenotic segments of the large arteries only when serotonin-2 receptor blockade with ketanserin and cyclo-oxygenase inhibition with aspirin were combined. RESULTS In the area of the stenosis and in the post-stenotic segment diameter increased 8.2% +/- 2.3% (P = .032) and 7.3% +/- 1.3% (P less than .001), respectively, when aspirin was combined with ketanserin. Significant changes did not occur in either the placebo group or in the group receiving only ketanserin. In the area of stenosis, there was a good correlation between the relative baseline narrowing of the vessel and its vasodilatation after combined ketanserin and aspirin (r = .689; P = .002). Vasodilatation at the level of arterial collaterals also was significantly more pronounced when the combination was used (P less than .001). CONCLUSIONS These findings suggest a component of vasoconstriction related to the deposition of activated platelets in stenotic segments of the large arteries in atherosclerosis.