Intermittent positive pressure ventilation (IPPV) delivered via nasal access can normalize alveolar ventilation for individuals with chronic alveolar hypoventilation (CAH) due to neuromuscular disease, spinal cord injury, or skeletal deformity. The purpose of this study was to evaluate the effect of nasal IPPV (NIPPV) air leakage-associated oxyhemoglobin desaturations (dSATs) on the sleep efficiency of kyphoscoliotic individuals with severe pretreatment nocturnal dSATs. Only individuals using nocturnal NIPPV without supplemental oxygen therapy were studied. Seven such individuals were able to maintain PaO2 greater than 60 mm Hg without supplemental oxygen therapy (five had been using oxygen therapy in the pretreatment period), had fewer hospitalizations, and had improvements in symptoms, arterial blood gas values, and nocturnal oxyhemoglobin saturation (SAT) by nocturnal NIPPV. This occurred despite polysomnographically observed sleep disruption and sleep stage changes associated with frequent transient dSATs and massive insufflation leakage. Arousals and dSATs were most frequent during rapid eye movement (REM) sleep with the latter occurring at a frequency of 10/h. The dSATs resulted in brief arousals or lightening of sleep stage 76% of the time. With or without arousal, central nervous system mediated reflex muscular activity occurred to diminish leak and normalize SAT. We conclude that the effectiveness of nocturnal NIPPV is dependent in part on central mediated muscular activity.