OBJECTIVE: The purpose of present study was to evaluate the acute effects of bi-level positive airway pressure (BiPAP) on heart rate variability (HRV) of stable chronic obstructive pulmonary disease patients (COPD). METHODS: Nineteen males with COPD (69+/-8 years and with forced expiratory volume in 1s <50% of predicted) and eight healthy sedentary age-matched (69 years) males in the control group (CG) were evaluated during two conditions of controlled respiratory rate: spontaneous breathing (SB) and BiPAP (inspiratory and expiratory levels between 12-14 cmH(2)O and 4-6 cmH(2)O, respectively). Peripheral oxygen saturation (SpO(2)), end-tidal of carbon dioxide (ETCO(2)), systolic blood pressure (SBP) and R-R interval were obtained. HRV was analyzed by time (RMSSD and SDNN index) and frequency domains (high frequency - HF, low frequency - LF and HF/LF ratio). RESULTS: Significant reduction of ETCO(2) and SBP in both groups and increase of SpO(2) in COPD group was observed during BiPAP ventilation (p<0.05). During spontaneous breathing, patients with COPD presented lower values of LF, LF/HF and higher values of HF when compared to CG (p<0.05). However, HF was significantly reduced and LF increased during BiPAP ventilation (58+/-19-48+/-15 and 41+/-19-52+/-15 un, respectively) in COPD group. Significant correlations between delta BiPAP-SB (Delta) ETCO(2) and DeltaHF were found (r=0.89). CONCLUSIONS: Sympathetic and parasympathetic neural control of heart rate is altered in COPD patients and that BiPAP acutely improves ventilation, enhances sympathetic response and decreases vagal tonus. The improvement of ventilation caused by BiPAP was associated with reduced cardiac vagal activity in stable moderate-to-severe COPD patients.