The balance of sodium (Na⁺) and water is closely related because of the osmotic relationship between the two. Water balance is regulated by the antidiuretic hormone (ADH) from the posterior pituitary, and Na⁺ is regulated by aldosterone produced by the adrenal cortex.

Thirst is experienced when water loss equals 2% or more of body weight or when there is an increase in osmolality. Osmolality can be increased by either a reduction in water or an increase in Na⁺. Osmoreceptors are located in the hypothalamus and are stimulated by increases in osmolality and decreases in blood volume. Oral fluids increase blood volume and decrease osmolality. Osmoreceptor stimulation also causes an increased release of ADH, which then increases renal tubular permeability to water and increases its reabsorption. This causes an increased concentration of urine. If fluid (blood) volume is decreased, centrally located volume and pressure-sensitive receptors (baroreceptors) are stimulated, which also stimulates the release of ADH.

Na⁺ is the most powerful cation in extracellular fluid (ECF), and chloride is the most powerful ECF anion. In addition to its primary role in maintenance of osmolality, Na⁺ also helps to maintain neuromuscular irritability, acid-base balance, various cellular chemical reactions, and membrane transport. Chloride (Cl⁻) neutralizes the positive charge of Na⁺ and is passively transported along with the active transport of Na⁺. Bicarbonate is the other major ECF anion, and its concentration varies inversely with that of Cl⁻.