Radiofrequency catheter ablation (RFCA) in dog triggers myocardial nerve sprouting and sympathetic hyperinnervation. It is possible that RFCA in humans has the same effects. To test the hypothesis that RFCA increases plasma nerve growth factor (NGF) concentration, we prospectively studied 24 patients (18 male, age 51짹9 years) who underwent RFCA for paroxysmal supraventricular arrhythmias, atrial fibrillation and ventricular arrhythmia (N=1). The average procedure times were 136 min in atrioventricular reciprocating tachycardia (N=3), 187 min for atrial flutter (N=2), 258 min for atrial fibrillation (N=18) and 240 min for ventricular tachycardia (N=1). Blood samples were obtained from the peripheral veins immediately before and after ablation, and again at different time points after ablation. The plasma level of NGF was determined with Enzyme-linked immunosorbent assay (ELISA). Results showed that the NGF plasma concentration (ng/ml) was 16짹15 (N=24) and 14짹10 (N=24) immediately before and after ablation (P=NS), and was 31짹20 (N=21, p< 0.001) the day after ablation. The NGF levels (ng/ml) were 26짹17 (N=20, p<0.001 compared with ablation day), 22짹11 (N=16, p=0.004), 29짹18 (N=11, p=0.0154), 39짹22 (N=3), 30짹5 (N=2) and 34 (N=1) at post-operative days 2-7, respectively. There were no significant correlations between NGF concentrations and the duration of ablation procedures or the duration of fluoroscopy. We conclude that RFCA in humans is followed by a two-fold increase of systemic NGF concentration within one day after ablation and persisted for a week afterwards. The increased NGF concentration suggests that RFCA can trigger cardiac nerve sprouting in humans