Fast motility of outer hair cells (OHC) is thought to be based on a hydromechanic principle. In vitro, the function of OHCs can be disturbed by a change in the osmolarity of the culture medium. Whether changes in the serum osmolarity in vivo can also interfere dth OHC motility has not been investigated as yet. Serum osmolarity of New Zealand White rabbits (n = 18) was elevated by a continuous infusion of glucose 40%, decreased by an infusion of aqua dest, or kept constant by an infusion of saline. OHC function was monitored using distortion products of otoacoustic emissions (DPOAE). Input:output curves were established between 2 and 5 kHz (geometric mean of f2) with primaries of levels between 35 and 55 dB SPL. Cochlear perfusion was measured using a fluorescence microsphere method. Elevation of the serum osmolarity from 306 +/- 17 mosm/l to 365 +/- 23 induced a decrease of DPOAE between 3 and 12 dB SPL. Cochlear blood flow increased from 0.11 +/- 0.09 to 0.15 +/- 0.10 ml/min/g. When decreasing the serum osmolarity from 303 +/- 9 to 281 +/- 8 mosm/l, only slight changes of the DPOAE could be verified. As in the control group, cochlear perfusion was almost unchanged. In the control group, neither serum osmolarity nor DPOAE changed. Comparable to findings in vitro, increasing the serum osmolarity can lead to a disturbance of OHC function. In patients suffering from sudden hearing loss, dehydration due to physical or mental stress is often observed. This new and promising pathophysiological concept needs further clinical evaluation.