Inability to maintain the upright position is manifested by a number of symptoms shared by either human pathophysiology and conditions following weightlessness or bed rest. Alterations of the neural sympathetic cardiovascular control have been suggested to be one of the potential underlying etiopathogenetic mechanisms in these conditions. We hypothesize that the study of the autonomic profile of human orthostatic intolerance syndromes may furnish a valuable insight into the complexity of the sympathetic alterations leading to a reduced gravitational tolerance. In the present paper we describe abnormalities both in the magnitude and in the pattern of the sympathetic neural firing observed in patients affected by orthostatic intolerance, attending the upright position. Also, we discuss similarity and differences in the neural sympathetic mechanisms regulating the cardiovascular system during the gravitational stimulus both in clinical syndromes and in subjects returning from space.