We have compared the effects on breathing of inspiratory mechanical support during wakefulness and sleep in healthy subjects. Nine awake volunteers breathed through a nose mask connected to a machine supplying variable levels of inspiratory positive airway pressure (IPAP). Tidal volume (VT), breath duration (TTOT) and end-tidal PCO2 (PETCO2) were measured over 1 min steady state periods with IPAP set at a minimal level (approx. 2 cmH2O) and at approx. 10 cmH2O. This protocol was repeated in 6 of the subjects during non-REM sleep. When awake, "10 cmH2O IPAP" caused a significant increase in mean VT from 513 to 842 ml and a significant fall in PETCO2 from 39.7 to 32.7 mmHg. During sleep, "10 cmH2O IPAP" caused no significant changes in VT (388 to 390 ml) or PETCO2 (41.8 to 39.8 mmHg). In each state, "10 cmH2O IPAP" had no significant effect on TTOT. Three subjects repeated the protocol with diaphragmatic surface EMG recorded as an index of efferent inspiratory activity. "10 cmH2O IPAP" had no consistent effect on EMG when awake but caused a reduction in each subject during sleep. We conclude that during non-REM sleep, inspiratory mechanical support is associated with a compensatory decrease in efferent inspiratory activity to achieve a similar tidal volume with maintenance of arterial PCO2. When awake, a "wakefulness drive to breathe" may be associated with maintained inspiratory activity such that mechanical support results in an increased tidal volume despite a fall in arterial PCO2.