The purpose of the current study was to investigate the nature of the interaction between the central and peripheral chemoreflex loops in humans, using the different speeds of response of the central and peripheral chemoreceptors to enable a temporal separation of their chemical stimulation. Subjects were exposed to an end-tidal Pco2 of 8-10 torr (1 torr = 1 mmHg = 133.3 Pa) above resting Pco2, with end-tidal Po2 = 100 torr, for 8 min. Thirty seconds after the hypercapnic stimulus was withdrawn, a 5-min hypoxic stimulus (end-tidal Po2 = 50 torr) was introduced. The 30-s interval was believed to be sufficient time for the peripheral chemoreceptors to adapt to the new level of carbon dioxide. Over the subsequent 5 min of hypoxia, however, the central chemoreceptors were exposed to diminishing hypercapnia. The response to the hypoxic step was compared with the effect of the same hypoxic step without the preceding period of hypercapnia. In 4 of the 5 subjects studied, the ventilatory response to hypoxia was unaffected by relative hypercapnia at the central chemoreceptor, suggesting that the central and peripheral chemoreflexes were independent of each other.