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Aim: To investigate whether the increasing CD40-CD40 ligand system is related to restenosis in patients after percutaneous coronary intervention (PCI). Methods:Twenty normal controls and 120 patients with PCI were investigated. The expres-sion of CD40 and the CD40 ligand (CD40L) on platelets was analyzed by indirect-immunofluorescence flow cytometry. The serum level of soluble CD40L (sCD40L) and C-reactive protein (CRP) was determined by commercially available enzyme linked immunosorbent assay. Restenosis was observed in 120 patients within a 6 month follow-up period after PCI surgery. Results: Restenosis occurred in 29 patients (24.2%). Patients who developed restenosis showed higher levels of CD40-CD40L system compared with non-restenotic patients before PCI. All restenotic patients showed a significant increase in CD40 [66.93:4.8, mean fluores-cence intensity (MFI)] and CD40L (14.9±1.8, MFI) co-expression on platelets as well as sCD40L (13.7+1.7 ng/mL) compared with non-restenotic patients and con-trois during the 6 month follow-up period (P<0.01). Elevated sCD40L and CD40L were significantly correlated with the serum level of CRP after percutaneous transluminal coronary angioplasty and with lumen loss during the 6 month follow-up period. Conclusion: The level of CD40L was associated with late restenosis after PCI indicating that restenosis is an inflammatory disorder.