The caudal parapyramidal area of the rat brain contains a population of neurons that are highly sensitive to an increase in the extracellular hydrogen ion concentration ([H+]o). Some of them fire synchronously with respiration when [H+]o is increased. These chemosensitive neurons are located in the caudal ventrolateral medulla in a medial region, closest to the pyramidal tract, and a lateral region, beneath the lateral reticular nucleus. To assess the nature of medullary connections, biotinylated dextran amine injections were performed after recordings from the neurons had been completed. The injections were located within the areas containing serotonergic neurons of the caudal parapyramidal area. The injections within the medial and lateral parts of the caudal parapyramidal region revealed bilateral terminal fields of varicosities within the nucleus of the solitary tract and the ventral respiratory column. Efferent bilateral projections to the lateral paragigantocellular, lateral reticular, and inferior olive nuclei, as well as ipsilateral projections to medial and lateral caudal parapyramidal regions were also identified. Efferent projections towards the raphe obscurus from both medial and lateral caudal parapyramidal regions were found. Medial caudal parapyramidal regions also sent efferent projections towards the raphe pallidus, B1-B3 region, and to the dorsal and ventral parts of the medullary reticular nuclei. The detection of H(+)-sensitive neurons in the caudal parapyramidal area and their projections towards the nucleus of the solitary tract and to the ventral respiratory column, associated with respiratory regulation, indicate that this region could be an excellent candidate for central chemoreception.