Radiofrequency catheter ablation (RFCA) is a frequently performed procedure in patients with atrial fibrillation. Prior studies have shown that the RFCA may directly stimulate vagal afferents during the procedure, whereas the vagal tone assessed by heart rate variability (HRV) is lowered weeks after the RFCA procedure. The effects of RFCA performed in the left atrium on sympathetic nerve activity have not been assessed. In the present study, we hypothesized that RFCA would lower muscle sympathetic nerve activity (MSNA) during ablation and would raise MSNA 1 day postablation. A total of 18 patients were studied. In protocol 1 ( n = 10), electrocardiogram, blood pressure, and MSNA in the peroneal nerve were recorded through the RFCA procedure performed in the electrophysiology laboratory. In protocol 2, eight patients were studied before the procedure and 1 day postablation. RFCA led to a decrease in MSNA immediately after the procedure (25.4 +/- 3.2 to 17.2 +/- 3.8 bursts/min, P < 0.05). Cardiac parasympathetic activity was determined using indexes of HRV and increased during the procedure. One day postablation, MSNA was above baseline values (21.3 +/- 3.7 to 35.7 +/- 2.6 bursts/min, P < 0.05). HRV indexes of cardiac parasympathetic activity fell, and the HRV index of sympathovagal balance was not significantly altered. The results show that RFCA raised cardiac parasympathetic activity and decreased MSNA during the procedure. One day postablation, MSNA rose and cardiac parasympathetic activity fell. In addition, RFCA evokes differentiated sympathetic responses directed to the heart and skeletal muscles. NEW & NOTEWORTHY The effects of radiofrequency catheter ablation performed in the left atrium on muscle sympathetic nerve activity (MSNA) have not been assessed. The results of this study show that radiofrequency catheter ablation raised cardiac parasympathetic activity and decreased MSNA during the procedure. One day postablation, MSNA rose and cardiac parasympathetic activity fell. We speculate that the partial autonomic afferent denervation induces these effects on autonomic activity.