We used rebreathing with prior hyperventilation to measure ventilatory responses to CO2 at iso-oxic PO2's of 100, 80, 60 and 40 mmHg in seven subjects. The mean sub-threshold ventilation (S.E.) of 7.60 (1.31) L min-1 did not vary with iso-oxic PO2. The mean peripheral-chemoreflex threshold of 41 (0.6)) mmHg PCO2 at an iso-oxic PO2 of 100 was greater than 39 (1.2) and 39 (0.6) at 60 and 40, respectively. The mean peripheral-chemoreflex sensitivity of 11.5 (5.2) L min-1 mmHg-1 at an iso-oxic PO2 of 40 was significantly greater than 3.0 (1.3), 2.7 (1.2) and 2.4 (1.2) at 60, 80 and 100, respectively. The mean central-chemoreflex threshold of 45 (1.5) mmHg PCO2 at an iso-oxic PO2 of 40 was significantly less than 48 (0.4) and 48 (0.7) at 80 and 100, respectively. The mean central-chemoreflex sensitivity of 5.0 (1.1) L min-1 mmHg-1 did not vary with iso-oxic PO2. These findings provide insights into the control of breathing in humans, including the implication that CO2 must exceed its peripheral-chemoreflex threshold before hypoxia can effectively increase ventilation.