In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation. One setting was aimed at maximally reducing arterial carbon dioxide tension (P(a,CO(2))) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean ± SD 27.6 ± 2.1 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 22 breaths · min(-1). The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7 ± 1.6 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 12 breaths · min(-1). Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (P(a,CO(2)) 59.3 ± 7.5, 55.2 ± 6.9 and 49.4 ± 7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure-time product of the diaphragm per minute from 323 ± 149 cmH(2)O · s · min(-1) during SB to 132 ± 139 cmH(2)O · s · min(-1) during Li-NPPV and 40 ± 69 cmH(2)O · s · min(-1) during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV. We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.