Long-term nocturnal nasal intermittent positive pressure ventilation (NIPPV) has beneficial effects on daytime PaCO2 in patients with chronic alveolar hypoventilation. Our aim was to investigate if these beneficial effects are related to improved respiratory drive as measured by ventilatory response to CO2. In 17 hypoventilated patients (mean age 62 years) we obtained daytime arterial blood gases, nocturnal transcutaneous oxygen saturation, nocturnal transcutaneous PaCO2 ventilatory response to CO2 re-breathing, spirometry and indices of respiratory muscle strength before and after 9 months of NIPPV. Patients served as their own controls. After 9 months of NIPPV day-time PaCO2 decreased from 7.1 kPa to 6.3 kPa, (P<0.001) and PaO2 increased from 8.1 kPa to 9.3 kPa, (P<0.01). The changes in morning and daytime PaCO2 and in nocturnal transcutaneous oxygen saturation were significantly correlated to the changes in several variables derived from the ventilatory response to CO2 re-breathing. In patients with substantial improvement in daytime PaCO2 we found significant improvements in ventilatory response to CO2 re-breathing. The present study confirms the beneficial effect of long-term NIPPV on daytime arterial blood gases. The results are consistent with the hypothesis that the improvement of daytime PaCO2 is related to improved respiratory drive observed after NIPPV.