The autonomic tone has been shown to influence the duration of the QT interval, however the independent contribution of sympathetic and parasympathetic tone is not fully elucidated. The influence of autonomic tone on QT duration was studied in 10 young healthy volunteers by evaluating the changes in QT and RR duration induced by i.v. isoproterenol infusion and by standing before and after i.v. administration of propranolol or atropine. Furthermore, the relationship between RR interval and QT duration was evaluated during nocturnal sinus arrhythmia and submaximal exercise test. Low doses of isoproterenol reduced RR (p < 0.01) but not QT interval duration, while higher doses influenced both RR (p < 0.0001) and QT (p < 0.001) duration. Propranolol did not influence standing-induced shortening of RR and QT intervals; on the contrary, atropine administration abolished standing-induced QT interval shortening, without influencing RR changes. QT duration resulted significantly related to preceding RR interval at peak exercise (r = 0.87, p < 0.001) and during nocturnal sinus arrhythmia (r = 0.73, p < 0.0005), however, the regression lines showing the correlation between QT and preceding RR interval were different. Both sympathetic and parasympathetic tone appear to contribute to heart rate-independent changes in QT duration. In the basal state parasympathetic more than sympathetic tone influences the relation QT-heart rate. Major increases of sympathetic nervous system activity may change the relation QT-heart rate. Thus, in case of abrupt autonomic changes, any proposed formula for heart rate correction of QT may result inappropriate, also in the normal range of heart rate.