The effects of TTS-scopolamine, dimenhydrinate, lidocaine, and tocainide on motion sickness and vertigo and on caloric and postrotatory nystagmus were evaluated in healthy volunteers. TTS-scopolamine was administered transdermally (delivering approximately 10 micrograms X h-1 scopolamine base) and 100 mg dimenhydrinate orally. Lidocaine and tocainide were administered intravenously (average plasma concentration of lidocaine 6 mol X L-1 and of tocainide 20 mol X L-1). TTS-scopolamine and dimenhydrinate significantly reduced vertigo induced by calorization of the ears, nausea provoked with Coriolis maneuvre, and nystagmus in caloric and rotatory tests. During treatment with lidocaine and tocainide no alleviation of vertigo and nausea was observed. Caloric nystagmus was reduced but rotation induced nystagmus was virtually unchanged. Presumably the motion sickness drugs act at the brain stem where TTS-scopolamine and dimenhydrinate have their target cells in the vestibular nuclei. Furthermore, the alleviation of motion sickness was linked to a decline of nystagmus. Lidocaine and tocainide, the action of which in vertigo and nausea in patients is proposed to be on the vestibular end organs and the supratentorial brain structures, consistently failed to alleviate motion sickness.