BiPAP ventilatory assistance can increase minute ventilation and reduce respiratory effort, but does not always reduce PaCO2. We studied the effects of BiPAP ventilatory assistance on PaCO2 and examined specific mechanisms whereby BiPAP ventilatory assistance may not lower PaCO2. BiPAP ventilatory assistance using a non-rebreather valve and volume cycled ventilation at similar settings produced significantly lower PaCO2 than BiPAP ventilatory assistance using a standard exhalation device. The failure of PaCO2 to fall with the standard exhalation device was due to exhalation past the exhalation device into the ventilator tubing, subsequent rebreathing of the exhaled gases, and an increase in dead space ventilation. Use of other fixed-resistance exhalation devices also resulted in exhalation back into the ventilator tubing. Use of a new plateau exhalation device or a non-rebreather valve eliminated CO2 rebreathing and its effect on dead space ventilation. Changing exhalation devices had no significant effect on BiPAP pressure generation or sensing capabilities. Our results indicate that the use of a standard exhalation device during BiPAP ventilatory assistance causes CO2 rebreathing, which can blunt any effect of BiPAP on PaCO2. Use of an appropriate alternative exhalation device can eliminate this problem.