The efficacy of negative pressure ventilation (NPV) in alleviating sleep-induced reductions in alveolar ventilation and in producing long-term clinical benefits was studied in 5 patients (54 +/- 8 yr of age; mean +/- SD) with chronic respiratory failure secondary to restrictive ventilatory impairment (VC, 40 +/- 14% predicted; TLC, 72 +/- 18% predicted; FEV1/FVC, 89 +/- 15%). In control sleep studies, arterial O2 saturation decreased from 81 +/- 6% during wakefulness to 79 +/- 1% during non-REM sleep and to 67 +/- 3% during REM sleep, and transcutaneous PCO2 increased from 80 +/- 16 mm Hg during wakefulness and non-REM sleep to 87 +/- 16 mm Hg during REM sleep. Nocturnal NPV in a cuirass ventilator improved baseline ventilation during wakefulness and prevented deterioration of alveolar ventilation during sleep. Upper airway obstruction during sleep induced by NPV was successfully managed with either a tricyclic medication or nasal CPAP. After 8 wk of nocturnal NPV, all patients felt considerably better. Daytime resting arterial PCO2 decreased from 56 +/- 2 to 46 +/- 3 mm Hg (p less than 0.05) and PO2 increased from 51 +/- 9 to 70 +/- 10 mm Hg (NS). Four patients have continued NPV at home on a regular basis and have returned to full-time employment. We conclude that nocturnal NPV is an effective method of preventing sleep-induced reductions in alveolar ventilation and a practical method of long-term management of patients with nonobstructive chronic respiratory failure.