Hypercapnia has been accepted during nasal intermittent positive pressure ventilation (nIPPV) and during subsequent spontaneous breathing in patients with chronic hypercapnic respiratory failure (HRF) due to COPD. We tested the hypothesis that nIPPV aimed at normalizing PaCO2 will reduce PaCO2 during subsequent spontaneous breathing. For that purpose 14 consecutive inpatients (age 61.4 +/- 9.9 years) with chronic HRF due to COPD were established on passive pressure-controlled nIPPV in a stepwise approach. Assisted ventilation with supplemental oxygen to reach normoxemia was started followed by passive ventilation with a stepwise increment in the inspiratory pressure and finally by a stepwise increase in the respiratory rate to establish normocapnia. Baseline pulmonary function parameters were: FEV1 0.97 +/- 0.43 l, PaCO2 59.5 +/- 8.4 mmHg, PaO2 49.9 +/- 7.8 mmHg, HCO3- 35.6 +/- 5.2 mmol/l, pH 7.39 +/- 0.04. Normoxemia as well as normocapnia was thus established by decreasing PaCO2 by 19.5 +/- 7.0 mmHg during nIPPV within 8.8 +/- 3.8 days (P < 0.001) (inspiratory pressure 29.8 +/- 3.8 mmHg, respiratory rate 22.9 +/- 1.9 BPM). Spontaneous PaCO2 measured 4 h after cessation of nIPPV decreased to 46.0 +/- 5.5 mmHg (P < 0.001), and HCO3- decreased to 27.2 +/- 3.0 mmol/l (P < 0.001). At 6 months of follow-up, II patients continued nIPPV with stable blood gases and with a decrease of P0.1/Plmax from 9.4 +/- 4.3% to 5.9 +/- 2.0% (P < 0.005). In conclusion, normalization of PaCO2 by passive nIPPV in patients with HRF due to COPD is possible and leads to a significant reduction of PaCO2 during subsequent spontaneous breathing and is associated with improved parameters of respiratory muscle function.