Previous studies have shown that noninvasive positive pressure ventilation (NPPV) improves gas exchange in acute and chronic respiratory failure. However, some patients are unable to tolerate NPPV due to air leaks around the mask, facial discomfort, and claustrophobia. A new mask that covers the entire face (Total, Respironics, Monroeville, Pa), attempts to overcome these obstacles. We studied the efficacy of NPPV via the Total face mask (TFM) in nine patients with chronic respiratory failure. In three patients, respiratory failure was due to chronic obstructive lung disease, and in six patients, it was secondary to restrictive disorders. None of the patients were previously able to tolerate NPPV via nasal (N) or nasal-oral (NO) masks. At baseline, all patients had impaired gas exchange with low PaO2/FIO2 (241 +/- 14), elevated PaCO2 (79 +/- 5 mm Hg), and poor functional status (1.89 +/- 1.45, on a scale of 1 to 7). After NPPV in the hospital for 7.1 +/- 1.5 h per night for 22 +/- 26 days, the PaCO2 fell to 59 +/- 3 mm Hg, and the PaO2/FIO2 rose to 304 +/- 27. Following nocturnal NPPV via the TFM for 6.7 +/- 1.5 h a night 6 +/- 5 weeks after hospital discharge, sustained improvements in PaCO2 (58 +/- 3 mm Hg, p < 0.05), PaO2/FIO2 (304 +/- 18), and functional status (5.38 +/- 1.06, p < 0.05) were observed. In four patients, measurements of respiratory rate, tidal volume, minute ventilation, dyspnea, discomfort with the face mask, and mask and mouth leaks were made during 30-min sessions of NPPV applied at constant levels via all three masks (N, NO, TFM). Discomfort with the face mask (0.38 +/- 0.18 vs 1.44 +/- 0.34 vs 2.38 +/- 0.32, p < 0.05) and mask leaks (0.44 +/- 0.18 vs 1.89 +/- 0.39 vs 1.89 +/- 0.35, p < 0.05) were least during NPPV via TFM compared with the N or NO masks, respectively. Moreover, expired tidal volume was highest (804 +/- 10 vs 498 +/- 9 vs 537 +/- 13 ml, p < 0.05) and PaCO2 lowest (51 +/- 2 vs 57 +/- 2 vs 58 +/- 3, p < 0.05) during NPPV via the TFM compared with N or NO masks. We conclude that NPPV delivered via a Total mask ensures a comfortable, stable patient-mask interface and improves gas exchange in selected patients intolerant of more conventional N or NO masks.