This chapter gives a brief history of the discovery of sympathoinhibitory vasomotor neurons in the caudal ventrolateral medulla and then addresses particular aspects of their function by reviewing published work and presenting new experimental evidence. The definition of inhibitory vasomotor neuronal groups within the medulla oblongata is a relatively recent achievement, facilitated by advances made in neuroanatomical methodology. A new generation of functional studies utilized focal intramedullary injections of pharmacological agents known to excite or inhibit nerve cell bodies, thereby reducing the problems of interpretation because of effects on the fibers of passage. The injection of L-glutamate into the caudal ventrolateral medulla in anaesthetized rabbits, rats, and cats caused a dramatic fall in arterial pressure, accompanied by the inhibition of peripheral sympathetic vasomotor tone. The possible physiological importance of this observation was emphasized by the ability of neuroinhibitory agents to increase arterial pressure when injected into the same region of the caudal ventrolateral medulla. In particular, muscimol, a long acting gamma aminobutyric acid (GABA) receptor-stimulating agent, caused a major increase in arterial pressure, sometimes associated with cardiac arrhythmias and pulmonary congestion. These observations suggested that the vasodepressor neurons are tonically active, at least in the anaesthetized animal.