Background: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all-cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age-related changes in measures of ventricular repolarization are not well characterized. Methods: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)-38 young subjects with a mean age of 28 +/- 4 years and 18 old subjects with a mean age of 71 +/- 7 years. QToD and T wave complexity were computed from 12-lead ECGs using the GE Marquette QT Guard automated analysis program with manual over-reading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. Results: Young males had a significantly greater QToD than young and old females at baseline (28 +/- 5 ms, 23 +/- 5 ms, and 22 +/- 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. Conclusions: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology.