Avian intrapulmonary chemoreceptor activity is reduced by increasing airway PCO2 from 0 to 60 torr. Using extracellular electrodes, we recorded discharge of individual intrapulmonary chemoreceptor cell bodies in the left nodose ganglion of the rooster (Gallus domesticus) during unidirectional ventilation of the lungs. All receptors recorded were in the left lung. To vary pulmonary arterial PCO2 independently of ventilation, we ventilated the two lungs separately and supplied the left pulmonary circulation with systemic arterial blood. When the PCO2 in the pulmonary arterial blood was increased, discharge frequency decreased in all 21 receptors studied. Sensitivity to pulmonary arterial PCO2 was similar to sensitivity to airway PCO2. When PCO2 of ventilatory gas was lower than that of pulmonary arterial blood, discharge frequency of the receptor increased when pulmonary blood flow was stopped. Discharge frequency also increased when PCO2 at the receptor site was lowered by increased ventilatory gas flow. We conclude that intrapulmonary chemoreceptors respond to the delivery and removal of CO2 by blood and ventilatory gas. This suggests that the receptors are located within the respiratory gas exchange region of the lung. Because these receptors have a strong inhibitory effect on ventilation, they may serve to (1) adjust minute ventilation to the rate of metabolic CO2 production and (2) to regulate individual breath size.