Background and ObjectivesZZAlthough the role of aquaporin-2 (AQP2) in the kidney has been well defined, its role in the inner ear remains to be determined. The present study was to investigate the effect of water deprivation on the expression of AQP2 in the inner ear. Materials and MethodZZHealthy male guinea pigs weighing 250 g were used. The experimental group underwent water restriction and the control underwent water loading with sucrose-containing water for 3 days. Concentrations of plasma arginine-vasopressin (AVP ) were determined and electrocochleography (ECoG) recordings were made. An RT-PCR, real-time PCR and Westernblotting analysis were used for quantitative analysis of AQP2 mRNA and AQP2 protein expression. Immunohistochemistry was also used to evaluate the distribution of AQP2 water channel proteins in the inner ear. ResultsZZAQP2 was mainly expressed in the epithelium of endolymphatic sac, spiral limbus, spiral ligament and stria vascularis of scala media. The concentrations of plasma AVP were 9.2± 0.8 pg/mL in the experimental group and 0.78±0.3 pg/mL in the control. The summation potential/ action potential (SP/AP) ratio in ECoG was markedly increased in the experimental group (0.55 in the experimental and 0.29 in the control). RT-PCR and real time PCR as well as Western blot analysis showed that the level of AQP2 mRNA and protein in the cochlea and endolymphactic sac of the water-deprived group was significantly higher than those in the control group. ConclusionZZThese data suggest that AQP2 is one of the important water channels in fluid homeostasis in the inner ear. Moreover, the volume of endolymphatic space can be increased via AVP-AQP2 system in response to water deprivation. Korean J Otorhinolaryngol-Head Neck Surg 2009;52:572-8 Key WordsZZAquaporin 2·Endolymphatic hydrops·Arginine vasopressin·Inner ear.