Background:This study was designed to evaluate the effects of autonomic tone on the QT interval, using conventional and heart rate independent analysis. Effects of autonomic tone on the QT interval have been studied either using rate correction formulae or during fixed rate atrial pacing, both of which have been associated with problems. Since most autonomic interventions are associated with heart rate changes, separation of “true” autonomic effects from rate related effects on the QT interval is essential.Methods:Electrocardiographic recordings were performed in 14 healthy volunteers during: (1) sympathetic stimulation (tilt, epinephrine infusion, isoproterenol infusion, and exercise); (2) β‐adrenergic blockade; (3) parasympathetic blockade; (4) autonomic blockade; (5) tilt following autonomic blockade; (6) parasympathetic stimulation (phenylephrine infusion); and (7) isolated α‐adrenergic stimulation (phenylephrine infusion following atropine). The QT interval was adjusted for heart rate using Bazett's formula. Heart rate independent analysis was performed between conditions with similar cycle lengths.Results:QT interval measurements were reproducible and exhibited the typical QT‐RR relationship. Sympathetic stimulation decreased the RR interval and prolonged the QTcinterval. Parasympathetic blockade also increased the QTc. Heart rate independent analysis of the effects of β‐blockade showed a shortening of the QT (from 368.5 ± 20.5 ms to 355.9 ± 17.9 ms; n = 8). Alpha‐adrenergic stimulation also decreased the QT interval from 302.4 ± 16.8 ms to 294.3 ± 17.7 ms (n = 7).Conclusion:Sympathetic stimulation prolongs the QT interval, while β‐blockade shortens it. Alpha‐adrenergic stimulation also shortens the QT interval. Autonomic effects on the QT interval as assessed by heart rate independent analysis may help separate the true autonomic effects