Although nasal continuous positive airway pressure (CPAP) is effective in the treatment of most patients with obstructive sleep apnea (OSA), there is a small group of such patients in whom rapid eye movement (REM) hypoventilation and CO2 retention persist despite the use of CPAP and supplemental oxygen. In this report we describe our experience with nocturnal nasal ventilation (nocturnal nasal positive pressure ventilation [NIPPV] in such patients and its effectiveness in reversing daytime hypercapnia. Thirteen patients, aged 28 to 69 years, with severe OSA confirmed on polysomnography, failed to respond to initial CPAP therapy. All were grossly obese (body mass index [BMI] > 35 kg.ml-1) and hypercapnic (mean PaCO2, 62 mm Hg). Nocturnal nasal ventilation was commenced using a volume-cycled ventilator, which was well tolerated in all patients. After 7 to 18 days of NIPPV, significant improvements in daytime arterial blood gas values were achieved, with a rise in arterial oxygen tension from 50 +/- 2.6 (SEM) to 66 +/- 3 mm Hg (p < 0.001) and a fall in CO2 from 62 +/- 2.5 to 46 +/- 1 mm Hg (p < 0.0001). Nine of the 13 patients were able to be established on a regimen of nasal CPAP after this period, while 3 patients required a longer period (up to 3 months) before adequate nocturnal ventilation could be maintained. In one patient, the improvements in ventilatory drive achieved with NIPPV could not be maintained on CPAP, and she was transferred on to NIPPV long term. These results indicate that effective nasal ventilation leads to an overall improvement in spontaneous ventilation and blood gas values both awake and asleep. We believe this improvement is the result of improved central ventilatory drive. Short-term NIPPV provides lasting benefits allowing the majority of such patients to resume CPAP therapy. Short-term intervention with this therapy should be considered as an interim measure in patients with severe hypercapnic OSA who fail to respond to initial CPAP therapy.