INTRODUCTION: The effect of an interval exercise training (ITE) program on heart rate variability (HRV) was studied in 8 patients with Charcot-Marie-Tooth (CMT) disease and 8 healthy controls. METHODS: At baseline, all subjects underwent ambulatory 24-hour Holter electrocardiographic (ECG) monitoring to evaluate HRV. HRV analysis was repeated on CMT patients after they completed a 24-week ITE program on a cycle ergometer. RESULTS: Before exercise, all HRV indices were lower in patients compared with controls, and the difference reached statistical significance for pNN50 (percent of differences between adjacent R-R intervals exceeding 50 ms). After ITE, time- and frequency-domain indices were significantly improved, particularly at night (+8% mean R-R interval, +95% pNN50, 52% reduction in low/high-frequency ratio). We observed significant increases in some of the time and frequency parameters, and values sometimes exceeded those of controls at baseline. CONCLUSIONS: Our results suggest that ITE improves HRV modulation in CMT patients by enhancing parasympathetic activity.