A prolonged QT interval in the neonatal period and during infancy is associated with higher mortality rates, independently of the appearance of symptoms. This suggests the opportunity of a prophylaxis with beta-blockers in this population. QT interval dispersion is a useful clinical tool to predict the efficacy of antiadrenergic therapy. However, the effects of antiadrenergic interventions on QT interval and QT interval dispersion in newborns are not known. Standard 12-lead electrocardiograms were recorded in 14 newborns with prolonged QT interval, before and after oral administration of 2 mg/kg propranolol. Two electrocardiograms were also recorded in 14 newborns with normal QT intervals, matched for age and sex. In the control group no differences in heart rate, mean QTc, and QTc dispersion between the two recordings were observed. In the newborns with prolonged QT interval, propranolol did not change mean Qtc (from 467 +/- 21 to 451 +/- 26 msec; difference not significant), whereas it decreased spatial QTc dispersion, measured as the difference between the longest and shortest QTc in 12 different leads (from 69 +/- 23 to 42 +/- 13 msec; -39%; p = 0.001). This reduction was explained mainly by a shortening of the maximum QTc (from 504 +/- 25 to 476 +/- 18 msec; p = 0.005), with no change in the minimum QTc, and was not dependent on the slight change in mean QTc, as shown by the decrease in the coefficient of variation of QTc (standard deviation of QTc/mean QTc x 100) from 6.0 +/- 2.2 to 3.3 +/- 0.8 (p = 0.002). Of note, after propranolol, both measures of QTc dispersion reached the same levels observed in the control newborns. During the follow-up (> 2 years for nine of 14 infants), none of the infants had symptoms or arrhythmias. These results suggest that beta-adrenergic blockade with propranolol slightly affects mean QTc, but it significantly decreases the spatial dispersion of ventricular repolarization in newborn infants with a prolonged QT interval. This effect might modify the arrhythmogenic substrate, leading to a reduction of the susceptibility to life-threatening arrhythmias.