Multiple system atrophy (MSA) provides a typical example of the integrative role of the central autonomic network in controlling cardiovascular, respiratory, bladder and gastrointestinal functions. There is increasing evidence that neurochemically defined neuronal groups of the brainstem are selectively affected in MSA to a much greater degree than in Parkinson's disease. These include the catecholaminergic neurons of the rostral ventrolateral medulla (C1 group) which project to the intermediolateral cell column and are involved in modulation of sympathetic vasomotor outflow, and noradrenergic neurons of the caudal ventrolateral medulla (A1 group) projecting to the magnocellular nuclei of the hypothalamus and regulating vasopressin (AVP) release. Loss of these groups of neurons may, at least in part, explain the development of orthostatic hypotension, baroreflex dysfunction, and impaired reflex AVP release in response to hypotension. There is preliminary evidence that cardiovagal neurons of the ventrolateral portion of the nucleus ambiguus, distinct from the branchimotor neurons of the compact region, may also be affected in MSA. Loss of cholinergic neurons in the medullary arcuate nucleus, considered by some to be the homologous to the central chemosensitive region of the ventral medullary surface, may contribute to disturbances in automatic ventilation, particularly during sleep, in patients with MSA.