The ventilatory response to venous CO2 loading and its effect on arterial CO2 tension was determined in five awake dogs. Blood, 200-500 ml/min, was diverted from a catheter in the right common carotid artery through a membrane gas exchanger and returned to the right jugular vein. CO2 loading was accomplished by changing the gas ventilating the gas exchanger from a mixture of 5% CO2 in air to 100% CO2. The ventilatory responses to this procedure were compared with those resulting from increased inspired CO2 concentrations (during which ventilation of the gas exchanger with the air and 5% CO2 mixture continued). The ventilatory response to each form of CO2 loading was computed as deltaVE/deltaPaco9. The mean ventilatory response to airway CO2 loading was 1.61 1/min per Torr PaCO2. The mean response for the venous CO2 loading was significantly higher and not significantly different from "infinite" CO2 sensitivity (i.e., isocapnic response). The results provide further evidence for a CO2-linked hyperpnea, not mediated by significant changes in mean arterial PCO2.