In the kidney, polarized epithelial cells play critical roles in ion, fluid and solute reabsorption from the ultrafiltrate to the blood supply. Detailed analysis of protein distributions has revealed that ion channels, transporters and pumps are restricted to distinct domains of the plasma membrane that face either the ultrafiltrate (apical membrane) or the blood supply (basal-lateral membrane). The importance of the development and maintenance of the polarized distributions of these proteins in renal epithelia for normal cell function is demonstrated by the fact that several disease states are characterized by abnormal distributions of proteins; for example in polycystic kidney disease, Na+/K(+)-ATPase has been detected in the apical and lateral membranes, compared with normal cells where Na+/K(+)-ATPase is localized in the basal-lateral membrane domain. Recent studies indicate that the development of restricted distributions of proteins at the cell surface of Madin Darby canine kidney epithelial cells is determined by direct sorting of proteins in the trans Golgi network into vesicles that are delivered vectorially to either the apical or basal-lateral membrane. Upon arrival at the plasma membrane, some proteins, such as Na+/K(+)-ATPase, may be selectively retained by binding to the membrane cytoskeleton.