A 53-year-old woman with a flaccid quadriparesis developed severe hyperventilation and respiratory alkalosis during pressure-support ventilation. A gas leak in the ventilator system caused a loss of positive end-expiratory pressure and autocycling of the ventilator. Large ventilator breaths were then delivered because a high level of pressure support was set in a patient with low respiratory impedance. The complication is rare and its occurrence requires a combination of patient and equipment factors. Awareness of the responsible factors will promote detection and prevention of the hazard.