We attempted to decrease PCO2 during noninvasive ventilation (NIV) and studied he effects of this therapy both in acute exacerbations of chronic obstructive pulmonary disease (COPD) and in its chronic state. Ninety six patients (63% male) with COPD and hypercapnia above 6.7 kPa were investigated. The mode and setting of the ventilator had to be chosen to achieve normocapnia. The subgroup of acute exacerbated COPD was separated by pH (<7.35=acute), by HCO3- (<26 mmol/l=acute), and by history (acute=history of recent deterioration). Ventilator settings were the following: tidal volume-972+/-137 ml and frequency-20+/-2.2 (volume preset). Inspiratory pressure was 33.6+/-14.2 mbar and frequency-19.7+/-5.1 (pressure preset). The preference of volume preset ventilators resulted from insufficient maximal pressures of the pressure preset devices. Eighty three percent of the patients became normocapnic while on NIV after 6.8+/-5.7 days. The mean PCO2 decreased from 64+/-13 mmHg to 41+/-6 mmHg (P<0.001). After 4 weeks, 72% of the patients were normocapnic while breathing spontaneously (P<0.001). The subgroups of acute exacerbation were the following: pH 28%, HCO3- 3.1%, and history 68%. All three indicators together were present in 2% of patients. Normocapnia under ventilation and during spontaneous breathing was independent from the subgroup. In conclusion, the study showed that normocapnia can be achieved in COPD under the ventilator and while breathing spontaneously in chronic and acute disease.