The magnitude of the osmotic fluid shifts between extracellular and intracellular compartments and the changes in solute concentration that follow a change in extracellular solute are determined by the following factors: (1) the rate constant of total body osmotic fluid transfer, (2) the change in the amount of solute per liter of initial extracellular volume, (3) the initial ratio of intracellular to extracellular volume, which is usually determined by the state of extracellular volume (for the same change in the amount of solute per liter of initial extracellular volume, the changes in both extracellular volume and osmolality are greater in edematous than nonedematous states) and (4) the initial osmolality of body fluids (comparatively, the lower the initial osmolality, the larger the osmotic fluid shifts will be). However, the magnitude of the change in osmolality will be the same regardless of initial osmolality, if the other determinants are the same. If the determining factors are known, formulae applied in clinical medicine to predict the changes in solute concentration are theoretically sound. The initial intracellular to extracellular volume ratio characterizes the state of body fluids and can be computed from the changes in solute concentration provided that osmotic equilibrium exists between intracellular and extracellular compartments before and after the osmotic disturbance.