The activation of platelets or leukocytes plays an important role in development of intimal hyperplasia. We investigated whether the local blood serotonin and soluble P-selectin levels changed during endovascular therapy of the iliac artery. Blood samples were obtained from the iliac artery of 18 lower limbs undergoing percutaneous balloon angioplasty alone (8 limbs, group I) or percutaneous balloon angioplasty and primary stenting (10 limbs, group II). The serotonin levels in platelet-poor plasma were measured in all limbs. In group I the urinary level of the serotonin metabolite 5-hydroxyindoleacetic acid was also measured 24 hours before and 24 hours after the procedures. The soluble P-selectin levels were measured in the 6 patients in group II. Before angioplasty the mean (+/- SEM) serotonin concentrations were 1.2 +/- 0.2, 1.2 +/- 0.4, and 1.2 +/- 0.3 ng/mL in all cases, group I, and group II, respectively. After angioplasty these values changed to 1.7 +/- 0.4 (P =.0750), 1.2 +/- 0.4 (P =.8001), and 2.1 +/- 0.6 ng/mL (P =.0529), respectively. In group I urinary 5-hydroxyindoleacetic acid concentrations 24 hours before and 24 hours after the procedures were 0.0026 +/- 0.0004 and 0.0031 +/- 0.0006 mg/mg creatinine, respectively (P =.2566). In group II the soluble P-selectin levels significantly increased after intervention, from 26.0 +/- 5.7 to 33.9 +/- 5.3 ng/mL (P =.0296). Although the serotonin levels did not change significantly, the soluble P-selectin levels increased significantly after intervention. Leukocyte activation may therefore contribute to the progression of restenosis after peripheral endovascular therapy.