Aquaporin-2 (AQP2) is present in the apical membrane of the kidney collecting duct and is regulated by vasopressin-dependent trafficking between the apical membrane and endosomal reservoirs. The molecular structure of AQP2 seems to be somehow different from that of AQP1 in that the third and fourth hydrophilic loops are significant in the formation of the aqueous pathway. The number of components that participate in the vasopressin-regulated trafficking machinery of AQP2 is increasing: Phosphorylation of AQP2 seems to be important; cytoskeletal components and vesicle-associated proteins play some role in the mechanism; many intracellular signal transduction systems are needed for proper regulation; and AQP2 gene regulation is significant in some pathophysiological status. Even with this background, much still needs to be elucidated.