To investigate the mechanisms by which human subjects prevent or compensate for the change in respiratory muscle length imposed by applying continuous positive pressure to the airways, six men were studied under general anesthesia with methoxyflurane at the end of a minor surgical procedure (rhinoplasty). Ventilatory and occlusion pressure response to carbon dioxide was measured by a rebreathing technique with no bias pressure, or with 16 cm H2O positive pressure produced by adding weights to a spirometer bell. Static pressure-volume curves of the respiratory system were obtained while the subjects were paralyzed with succinyl choline. In contrast to awake subjects described in other studies, the anesthetized patients did not activate expiratory muscles to combat the rise in end-expiratory level caused by pressure, and showed little evidence of enhanced activation of inspiratory muscles that in the conscious state compensates for the disadvantage of their shorter length. A change in the shape of the occlusion pressure wave, however, suggested that positive pressure had some effect on the neural discharge to inspiratory muscles. The mechanisms by which the respiratory system defends itself against a pressure load that tends to change end-expiratory level are sensitive to anesthesia and may require consciousness.