The role of extracellular fluid status and sodium balance in various forms of hypertension often has been difficult to define precisely because of the limitations of direct measurements of these factors. Isotopic measurements of various fluid volume compartments in the body have suffered from being insensitive and imprecise. Estimates of sodium content have also been difficult because of the ready diffusion of this ion among many body compartments. Studies of sodium balance utilizing metabolic ward techniques have been too time-consuming and arduous for large-scale investigations. Thus, inferences on the role of sodium and volume in blood pressure have been derived largely from indirect observations based on the response of blood pressure to manipulation of sodium or volume status, or both, and by changes in dietary sodium, or administration of intravenous sodium loads or diuretics. Such studies, while indirect and often crude in precision, have yielded important new insights into the etiology and pathogenesis of hypertension. The roles of agents that influence renal handling of sodium and water, and vascular biology are also being investigated for their influence on sodium homeostasis.