Control of cell size within defined limits is vital for maintenance of normal organ function. This important feature of cell physiology can be disturbed by changes in membrane transport in epithelial cells. In addition, fluctuations in the osmolality of the extracellular fluid, caused by an abnormal plasma concentration of sodium, glucose, or urea can lead to derangements in cell size. Cell volume regulation is especially important in the brain because the brain is confined within a non-compliant vault and cannot tolerate significant perturbations in cell size. Therefore, brain cells have developed a coordinated array of adaptive mechanisms designed to modulate the cytosolic content of osmotically active solutes in response to alterations in the osmolality of the extracellular fluid. This process is controlled by various hormones including arginine vasopressin, insulin, and estrogen, and is subject to changes during development. The bulk of the change in cell content of osmolytes involves inorganic electrolytes. However, excessive variation in the cytosolic ionic strength has deleterious effects on protein structure and enzyme function. Therefore, brain cells have developed the capacity to accumulate or extrude various organic osmolytes in order to adjust the cytosolic osmolality without adversely affecting cell function. These solutes are termed non-perturbing osmolytes and belong to one of three classes of molecules: amino acids, carbohydrates and polyhydric sugar alcohols, or methylamines. Cerebral cells regulate the cytosolic content of organic osmolytes primarily by altering the transmembrane flux of these solutes. There are features of the cell volume regulatory response that are shared by the brain and kidney cells.(ABSTRACT TRUNCATED AT 250 WORDS)