Immediately following spaceflight, many astronauts are unable to maintain adequate perfusion of the brain after assuming an upright posture; this condition is called post-spaceflight orthostatic intolerance (PSOI). Considerable evidence shows that inputs from otolith organs and other graviceptors play an important role in regulating blood pressure during changes in posture in a 1-g environment. However, reflexes elicited by graviceptors, presumably including those affecting the cardiovascular system, are attenuated during spaceflight. Thus, PSOI could be related to effects of microgravity on the processing of inputs from otolith organs and other graviceptors by the central vestibular system. It is likely that successful countermeasures for PSOI must address the plastic changes induced in the nervous system by changes in the patterns of graviceptive inputs that occur during spaceflight.