The purpose of this study was to measure the contribution of the peripheral chemoreceptor (pR) to VE during the steady-state of moderate-intensity cycle ergometer exercise using continuous hyperoxic suppression of pRc drive, while stabilizing the drive from the central chemoreceptor by clamping end-tidal PCO2 (PETCO2) at the peak level attained during the hyperoxic period of a poikilocapnic ride. In the isocapnic protocol, the PETCO2 was maintained at a constant level by a negative feedback, open loop system. Five subjects completed four repetitions of each of the poikilocapnic and isocapnic protocols. In the poikilocapnic protocol, VE declines following the step into hyperoxia and then began to increase, whereas the decline in VE was maintained in the isocapnic protocol. However, the mean decrease in VE was not significantly different between the poikilocapnic (16.1 +/- 5.0%) and isocapnic (14.9 +/- 4.4%) protocols. These results suggest that the declining phase of VE is fully complete before the secondary central stimulating actions of hyperoxia on VE and that the pRc contributes about 15% of the drive to breathe in moderate intensity exercise.