The present review has extended the general theory of motion sickness proposed by Wood and Graybiel [135, 136] by identifying specific neurophysiological mechanisms that are involved in motion sickness and by interpreting the actions of both scopolamine and amphetamine as effective anti-motion sickness drugs within this neurophysiological context. The neurochemical and neurophysiological effects of scopolamine have been reviewed in relationship to central cholinergic pathways. Cholinergic pathways have been associated with both the perception and expression of normal and excessive levels of motion stimuli. New approaches to the problem of the prevention of motion sickness have been considered. Efferent nicotinic innervation at the primary sensory hair cells and the medial vestibular nucleus were identified as sites where modulation by cholinergic drugs might exert a beneficial influence. However, it was generally conceded that the complexity of the cholinergic system and the interaction of scopolamine with that system left open the possibility that pharmacological doses of drugs specific to the cholinergic system might exert significant modulatory influences at alternative sites, as well.