As QT variability increases and heart rate variability diminishes, the QT variability index (QTVI) - a non-invasive measure of beat-to-beat fluctuations in QT interval on a single ECG lead - shows a trend towards positive values. Increased QT variability is a risk factor for sudden death. Aging lengthens the QT interval and reduces RR-interval variability. In the present study we investigated the influence of aging and the autonomic nervous system on QT-interval variability in healthy subjects. We studied 143 healthy subjects, and divided them into two age ranges (younger and older than 65 years). For each subject we measured two QTVIs: from the q wave to the end of the T wave (QTeVI) and to the apex of the T wave (QTaVI). Both indexes were calculated at baseline and after sympathetic stress. In 10 non-elderly subjects, both QTVIs were determined after beta-adrenoreceptor blockade induced by intravenous infusion of propranolol or sotalol. The QTVI was higher in elderly than in younger subjects (P<0.001). QTVIs obtained during sympathetic stress remained unchanged in the elderly, but became more negative in the younger group (P<0.05). QTeVI and QTaVI at baseline were correlated positively with age (P<0.01) and anxiety scores (P<0.05), but inversely with the low-frequency spectral power of RR-interval variability (P<0.001). QTVIs were higher in subjects with higher anxiety scores. In younger subjects, sotalol infusion increased both QTVIs significantly, whereas propranolol infusion did not. In conclusion, aging increases QT-interval variability. Whether this change is associated with an increased risk of sudden death remains unclear. The association of abnormal QT-interval variability with anxiety and with reduced low-frequency spectral power of heart rate variability merits specific investigation. In healthy non-elderly subjects, acute sympathetic stress (tilt) decreases the QTVI. beta-Adrenoreceptor blockade inhibits this negative trend, thus showing its sympathetic origin. Because a negative trend in QTVI induced by sympathetic stress increases only in younger subjects, it could represent a protective mechanism that is lost with aging.