The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. This nucleus is a mesencephalic structure of the amphibian brain and is probably homologous to the LC in mammals. There are no data available for the role of LC in the central chemoreception of amphibians. Thus the present study was designed to investigate whether LC of toads (Bufo schneideri) is a CO 2/H ϩ chemoreceptor site. Fos immunoreactivity was used to verify whether the nucleus is activated by hypercarbia (5% CO2 in air). In addition, we assessed the role of noradrenergic LC neurons on respiratory and cardiovascular responses to hypercarbia by using 6-hydroxydopamine lesion. To further explore the role of LC in central chemosensitivity, we examined the effects of microinjection of solutions with different pH values (7.2, 7.4, 7.6, 7.8, and 8.0) into the nucleus. Our main findings were that 1) a marked increase in c-fos-positive cells in the LC was induced after 3 h of breathing a hypercarbic gas mixture; 2) chemical lesions in the LC attenuated the increase of the ventilatory response to hypercarbia but did not affect ventilation under resting conditions; and 3) microinjection with acid solutions (pH ϭ 7.2, 7.4, and 7.6) into the LC elicited an increased ventilation, indicating that the LC of toads participates in the central chemoreception.ventilation; midbrain; brain stem; amphibian; isthmus; bufo; hypercarbia IT IS WELL ESTABLISHED THAT vertebrates display respiratory responses to changes in the arterial blood gases, and the underlying control mechanisms are very similar among different taxa. The transition of amphibians to air breathing was accompanied by an increase in the sensitivity to CO 2 /H ϩ (45). Interestingly, the ontogenetic changes of anuran amphibians involve modifications of the control system from being almost entirely oxygen driven to a combination of acid-base and oxygen driven (11).Central respiratory CO 2 chemoreceptors have been clearly established in adult anuran amphibians (8,46), and these receptors are probably distributed throughout the rostral medulla, surrounding the fourth ventricle (50). In mammals, these receptors were once thought to be located only close to the surface of the ventral medulla, but it is now clear that they are widespread within the brainstem (12). Recently, sites have been identified in the ventrolateral medulla, nucleus of the solitary tract, ventral respiratory group, locus coeruleus (LC), caudal medullary raphe, and fastigial nucleus of the cerebellum (for a review, see Ref. 35). However, it remains unclear whether chemoreceptors are also widely distributed in amphibians. An evaluation of specific contributions of these chemosensitive sites can be achieved by CO 2 challenge, focal stimulation, or focal disruption. Focal acidification of a single central chemosensitive site increases ventilation, whereas disruption decreases ventilation (3,28,37,47). According to Nattie (35), the presence of widespread central chemoreceptors may be related to the increased demands of a...