The independence of the central and peripheral chemoreflexes has been tested in humans. Acute metabolic acidosis generated by a prior bout of brief, hard exercise was used to stimulate primarily the peripheral chemoreceptors, and respiratory acidosis generated by inhaled CO2 was used to stimulate both central and peripheral chemoreceptors. Seven healthy young men were studied. Ventilation and arterial pH, PCO2 and PO2 were recorded. Peripheral chemoreflex sensitivity to hypoxia during acute metabolic acidosis was repeatedly determined by measuring ventilation in euoxia (PETO2 = 100 Torr) and hypoxia (PETO2 = 50 Torr) as the subject recovered from exercise-induced acidosis. Peripheral chemoreflex sensitivity to hypoxia during CO2 inhalation was repeatedly determined by measuring ventilation in euoxia and hypoxia at two levels of hypercapnia (PETCO2 = 45 Torr and PETCO2 = 50 Torr). The ventilatory sensitivity to hypoxia at matched arterial pH values was not significantly different between conditions of high (CO2 inhalation) and low (metabolic acidosis) central chemoreceptor activity. We therefore conclude that interaction between central and peripheral chemoreflexes was non-significant in all subjects.