Nearly every cell in the kidney can volume regulate in response to a hypertonic challenge. Some are able to respond immediately to hyperosmotic media by a RVI. Other cells require stimulation prior to exposure to hyperosmolarity to demonstrate RVI. An increase of intracellular osmolytes during RVI usually occurs by an increase of NaCl influx either via the activation of parallel Na(+)-H+ and Cl(-)-HCO3- exchangers, or Na(+)-K(+)-2Cl- cotransporters. Medullary and papillary cells use organic solutes as well to increase the intracellular concentration of osmolytes. In response to a hypotonic challenge, a RVD response has been demonstrated in the majority of the kidney cells. The efflux of solute during RVD is usually via K+ loss by activation of conductance pathways. Stretch-activated K+ channels and Ca2(+)-activated-K+ channels have been shown to be stimulated in cells exposed in hyposmotic solutions and could thus be involved in RVD. The accompanying anion loss is less well-defined but could be either Cl- or HCO3- in different segments of the nephron. In some cells, the reduction of intracellular solute content is via an efflux of organic osmolytes. Thus it appears that cells in all segments of the nephron volume regulate in response to osmotic stresses. This regulation may be an essential part of transepithelial transport since the cells have to survive transcellular fluxes of osmolytes. It may be particularly important in the kidney to control cell volume both in response to changes in osmolarity and transcellular fluxes of solute in order to maintain proper flow of fluid through the nephron.