The effect of the settings of inspiratory time and inspiratory flow during assist–control ventilation on the response of a patient's respiratory controller has been the subject of intense research during the last few years. An increase in inspiratory flow or a decrease in tidal volume delivered by the ventilator is associated with prompt increases in respiratory frequency. The changes occur before any change in arterial blood gases can take place. These responses occur both during wakefulness and sleep and in health and disease states. Whether the responses are the result of Hering-Breuer reflex activity or they arise in flow-sensitive receptors remains to be defined. Important clinical implications of the respiratory rate response to changes in ventilatory settings include effects on carbon dioxide, intrinsic positive end-expiratory pressure, and, possibly, on the instability of the respiratory rate in the transition between wakefulness and sleep.