The aim of the study was to resolve the issue of spaceflight-induced, adaptive modification of the otolith system by measuring unilateral otolith responses in a pre- versus post-flight design. The study represents the first comprehensive approach to examining unilateral otolith function following space flight. Ten astronauts participated in unilateral otolith function tests three times preflight and up to four times after Shuttle flights from landing day through the subsequent 10 days. During unilateral centrifugation, utricular function was examined by the perceptual changes reflected by the subjective visual vertical (SVV) and the otolith-mediated ocular counter-roll, designated as utriculo-ocular response (UOR). Unilateral saccular reflexes were recorded by measurement of collic vestibular evoked myogenic potentials (cVEMP). The findings demonstrate a general increase in interlabyrinth asymmetry of otolith responses on landing day relative to preflight baseline, with subsequent reversal in asymmetry within 2-3 days. Recovery to baseline levels was achieved within 10 days. This fluctuation in asymmetry was consistent for the utricle tests (SVV and UOR) while apparently stronger for SVV. A similar asymmetry was observed during cVEMP testing. In addition, the results provide initial evidence of a dominant labyrinth. The findings require reconsideration of the otolith asymmetry hypothesis; in general, on landing day, the response from one labyrinth was equivalent to preflight values, while the other showed considerable discrepancy. The finding that one otolith response can return to one-g level within hours after re-entry while the other takes considerably longer demonstrates the importance of considering the otolith response as a result of both peripheral and associated central neural processing.