Reduced vagal activity has been demonstrated to be associated with an increased risk of sudden death. Assessing the heart rate variability as a measure of the autonomic control of the heart has been established as a useful tool for the risk stratification of patients after myocardial infarction. In the current study, heart rate variability assessed by time- and frequency-domain measures was determined from Holter recordings before and during treatment with sotalol in 28 patients with chronic ventricular arrhythmias. The heart rate variability at baseline was independent of the presence or absence of spontaneous arrhythmias and of left ventricular function. Therapy with sotalol produced a significant improvement over control values in indices of parasympathetic tone (root mean square of the difference in successive RR intervals, proportion of adjacent RR intervals different by > 50 msec, high-frequency power spectrum). This improvement was not related to drug-induced changes in the mean heart rate or the suppression of ventricular ectopic activity. These effects on heart rate variability may contribute significantly to the overall efficacy profile of sotalol.