Arrhythmias in patients with repaired tetralogy of Fallot (ToF) might be due in part to altered autonomic heart rate control caused by altered right ventricle hemodynamics. This study investigated autonomic heart rate control in adolescents with ToF at rest and during unloading of the right ventricle. A total of 17 patients with ToF and 56 healthy controls aged 12 to 18 years underwent orthostatic stress with lower body negative pressure of -20 mm Hg. Heart rate, blood pressure, and stroke volume were recorded noninvasively. Indices of heart rate variability were computed in time and frequency domains. All patients with ToF also underwent cardiac magnetic resonance imaging, demonstrating pulmonary regurgitation and right ventricular dilation. At rest, heart rate variability indices of vagal heart rate control were nonsignificantly lower in the patients with ToF compared with controls. During lower body negative pressure, heart rate increased more in controls than patients with ToF (p <or=0.001). Further, most heart rate variability indices decreased in controls, but increased in patients with ToF (p <or=0.01 or p <or=0.001 for all variables), suggesting vagal activation in the patients with ToF. In conclusion, adolescents after ToF repair have fairly normal heart rate control at rest despite altered right ventricular hemodynamics. During unloading of the right ventricle, however, vagal heart rate control increases in the patients with ToF and decreases in the controls.