In hypoproteinemia, increased interstitial hydrostatic and decreased interstitial colloid osmotic pressures, together with increases in lymph flow, prevent interstitial fluid volume expansion, thus forming the edema-preventing mechanisms. Transfer of a substantial portion of the interstitial protein pool into the vascular compartment by increased lymph flow is the major edema-preventing mechanism. The increase in interstitial pressure during progressive interstitial fluid volume expansion is limited by the high compliance of the interstitium in most tissues. During hypoproteinemia low interstitial colloid osmotic pressure and high interstitial compliance permit augmented changes in plasma volume in response to rapid increases (orthostasis, venous constriction) and decreases (hemorrhage) in capillary pressure. Nevertheless, these same forces are responsible for the finding that during the relatively slow changes in sodium balance that occur during volume retention or after treatment with diuretics, the change in plasma volume is relatively small. These phenomena are illustrated by observations gathered in experimental hypoproteinemia and in patients with the nephrotic syndrome.