Amiodarone, a potent antiarrhythmic agent, has been shown to depress sinus node function. Therefore, this study was undertaken to assess the effect of chronic amiodarone therapy on heart rate during graded exercise testing. 13 patients treated with amiodarone for ventricular arrhythmias were administered symptom-limited graded exercise testing before and 12 weeks after drug therapy. None of the patients had prior evidence of sinus node dysfunction. The mean resting heart rate (beats per minute; bpm) before and after amiodarone therapy was 75 ± (SD) 13 versus 60 ± 7 bpm, respectively (p < 0.005), and the maximal heart rate was 135 ± 30 versus 109 ± 24 bpm (p < 0.005). However, the change in heart rate from rest to maximum exercise (heart rate reserve) was not affected by the drug. Heart rate measured at comparable exercise levels before and during amiodarone therapy was 124 ± 25 versus 104 ± 31 (p < 0.025). There was no change in the systolic blood pressure readings at these respective measured heart rates. Estimated maximal functional capacity before and after drug therapy was 4.9 ± 1.8 versus 4.7 ± 2.2 METs (p = NS). In conclusion, chronic amiodarone therapy significantly decreases heart rate at rest and during exercise without altering systolic blood pressure and functional capacity.