AIMS: Aim of this study was to investigate the number of circulating progenitor cells, systemic inflammatory mediators, and myocardial necrosis in patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation by radiofrequency (RF) ablation. Radiofrequency ablation generates a localized myocardial necrosis that might result in a release of inflammatory mediators enhancing progenitor cell mobilization and improving tissue repair. METHODS AND RESULTS: Blood samples were collected in patients with paroxysmal AF before and after PV isolation. Interleukin (IL)-6, IL-1beta, TNF-alpha, IL-8, IL-10, and IL-12, and stromal derived factor (SDF)-1 were measured by immunoassay. CD34+CD133+, CD117+, and endothelial progenitor cells (EPCs) were analysed by flow cytometry and culture assay. After ablation procedure, a rise in creatine kinase and troponin T levels indicated myocardial necrosis. Leukocyte counts and C-reactive protein and IL-6 levels increased significantly. Myocardial necrosis and inflammatory response correlated with an increase in IL-6 (P = 0.007). In contrast, SDF-1 levels decreased after RF ablation (P = 0.004). Yet, no significant changes were observed in IL-1beta, TNF-alpha, IL-8, IL 10, and IL-12 plasma levels or in the number of circulating CD34+CD133+ and CD117+ progenitor cells, whereas EPCs decreased by trend. CONCLUSION: Although PV isolation by RF ablation in patients with paroxysmal AF induces a systemic inflammatory response associated with myocardial necrosis, no alterations in circulating progenitor cells were observed. Thus, isolated myocardial necrosis may not be sufficient to account for progenitor cell mobilization.