A diverse group of processes are involved in central control of ventilation. Both fast acting neurotransmitters and slower acting neuromodulators are involved in the central respiratory drive. This review deals with fast acting neurotransmitters that are essential centrally in the ventilatory response to H(+)/CO(2) and to acute hypoxia. Data are reviewed to show that the central response to H(+)/CO(2) is primarily at sites in the medulla, the most prominent being the ventral medullary surface (VMS), and that acetylcholine is the key neurotransmitter in this process. Genetic abnormalities in the cholinergic system lead to states of hypoventilation in man and that knock out mice for genes responsible for neural crest development have none or diminished CO(2) ventilatory response. In the acute ventilatory response to hypoxia the afferent impulses from the carotid body reach the nucleus tractus solitarius (NTS) releasing glutamate which stimulates ventilation. Glutamate release also occurs in the VMS. Hypoxia is also associated with release of GABA in the mid-brain and a biphasic change in concentration of another inhibitory amino acid, taurine. Collectively changes in these amino acids can account for the ventilatory output in response to acute hypoxia. Future studies should provide more data on molecular and genetic basis of central respiratory drive and the role of neurotransmitter in this essential function.