BACKGROUND: Biventricular pacing is emerging as a long-term therapy for symptomatic heart failure. Analysis of heart rate variability (HRV) has become an important predictive tool in this syndrome. AIM OF THE STUDY: To assess whether chronic resynchronization therapy can affect HRV in patients with heart failure. METHODS AND RESULTS: Thirteen patients with heart failure were studied (mean age+/-1 S.E. 65+/-2.2 years, QRS 195+/-5.3 ms, NYHA class 3.2+/-0.1, LVEF 21+/-1.7%). The protocol included a preliminary no pacing period for 1 month following device implantation. Twenty-four hour Holter ECG recordings were performed at the end of this period (baseline) and after 3 months of biventricular stimulation (VDD mode). Prior to and following pacing patients underwent NYHA class evaluation, 6-min walk test, Quality of Life Assessment and a cardiopulmonary exercise test. Biventricular pacing improved functional class (P<0.0001) and Quality of life (P<0.0001), increased 6-min walk distance, (P=0.008) and exercise duration (P<0.0001) but had no significant effect on peak exercise VO(2). Resynchronization therapy increased mean 24-h RR (922+/-58 vs. 809+/-41 ms at baseline, P=0.006), SDNN (111+/-11 vs. 83+/-8 ms, P=0.003), SDNN-I (56+/-10 vs. 40+/-5 ms, P=0.02), rMSSD (66+/-14 vs. 41+/-8 ms, P=0.003), Total Power (5724+/-1875 vs. 2074+/-553 ms(2), P=0.03), Ultra Low Frequency Power (1969+/-789 vs. 653+/-405 ms(2), P=0.03) and Very Low Frequency Power (2407+/-561 vs. 902+/-155 ms(2), P=0.004). CONCLUSION: Biventricular pacing in heart failure improves autonomic function by increasing HRV. This may have important prognostic implications.