Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct(OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water and acid/base handling), analysis of OMCD hypertrophy (electron microscopy)and hyperplasia (PCNA labelling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium- depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (p<0.05) between the two libraries, 120 were over-expressed and 66 were down-regulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and -intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassiumdepletion: sodium, potassium and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.