Evidence is presented that the multisensory parieto-insular cortex is the human homologue of the parieto-insular vestibular cortex (PIVC) in the monkey and is involved in the perception of verticality and self-motion. Acute lesions (patients with middle cerebral artery infarctions) of this area caused contraversive tilts of perceived vertical, body lateropulsion, and, rarely, rotational vertigo. Brain activation studies using positron emission tomography or functional magnetic resonance tomography showed that PIVC was activated by caloric irrigation of the ears or by galvanic stimulation of the mastoid. This indicates that PIVC receives input from both the semicircular canals and otoliths. PIVC was also activated during small-field optokinetic stimulation, but not when the nystagmus was suppressed by fixation. Activation of vestibular cortex areas, visual motion-sensitive areas, and ocular motor areas exhibited a significant right-hemispheric dominance. The vestibular cortex intimately interacts with the visual cortex to match the two 3-D orientation maps (perception of verticality, room-tilt illusion) and mediates self-motion perception by means of a reciprocal inhibitory visual-vestibular interaction. This mechanism of an inhibitory interaction allows a shift of the dominant sensorial weight during self-motion perception from one sensory modality (visual or vestibular) to the other, depending on which mode of stimulation prevails: body acceleration (vestibular input) or constant velocity motion (visual input).