Arterial PO₂ and PCO₂ are maintained at constant levels by neural activity that controls breathing. Central respiratory drive is sensitive to changes in arterial PO₂ and PCO₂ which are monitored by the peripheral and central chemoreceptors. The role of purinergic signalling in central and peripheral mechanisms of chemosensitivity has been studied extensively in our laboratories over the last several years. Results obtained allow us to propose a unifying hypothesis of central (within the ventrolateral medulla of the brainstem) and peripheral (within the carotid body) chemosensory transduction, which involves ATP as a common mediator. Indeed, P2 receptors for ATP are expressed within the ventrolateral medulla (in particular by the respiratory neurones) as well as by the peripheral chemosensory afferent neurones which relay information to the brainstem. Blockade of the P2 receptors within the ventrolateral medulla attenuates the CO₂-induced increase in respiration while blockade of the P2X receptors in the carotid body (or their elimination in the knockout mice) greatly diminishes the ventilatory response to hypoxia and impairs carotid body function. ATP is released from the ventral surface of the medulla during hypercapnia and from the carotid body during hypoxia. Finally, exogenous ATP applied on the ventral surface of the medulla evokes rapid increase in respiration, while ATP applied to the carotid body evokes marked excitation of the carotid sinus nerve chemoafferents. We suggest that in the ventrolateral medulla ATP is produced following CO₂/H⁺-induced activation of central chemosensors (neuronal and/or glial) and acts within the respiratory network to produce physiologically relevant changes in ventilation. In the carotid body, ATP contributes in a significant manner to the transmission of the sensitivity of the carotid body to changes in arterial PO₂ and may be considered as a key transmitter released by chemoreceptor cells to activate endings of the sinus nerve afferent fibres.