We studied the effects of assisting respiration with inspiratory positive pressure (IPP) during air and CO2 breathing by measuring ventilatory and mouth occlusion (P0.1) responses in 15 normal human subjects. Switching from spontaneous breathing to IPP without added CO2 did not cause a significant change in mean Paco2, P0.1, or VI. During CO2 breathing, switching to IPP did not significantly alter tidal volume or frequency. The mean ventilatory response to CO2 during spontaneous breathing was 1.02 liters/min/mm Hg. With IPP at pressure limits of 5 and 7 cm H2O, the mean responses were 0.93 and 0.89 liters/min/mm Hg, respectively, not significantly different from spontaneous breathing. The mean spontaneous P0.1 response to CO2 was 0.32 cm H2O/mm Hg. With IPP at 5 and 7 cm H2O, the responses were 0.29 and 0.36 cm H2O/mm Hg, also not significantly different from spontaneous breathing. Reduction of muscular work of breathing by IPP in normal human subjects does not induce a measurable change in either respiratory drive or ventilation, which appear to remain dependent on chemoreceptor input. Inspiratory effort continues during IPP, even though it may be less than during spontaneous breathing.