Several lines of investigation have indicated the existence of abnormalities in salt and water metabolism in hypertensive cardiovascular disease. It has been shown, for example, that the electrolyte and water contents of the tissues in the hypertensive animal deviate from that in the normal (1) and that there is an increased rate of excretion of antidiuretic substance in the urine in experimental and human hypertension (2). The effect of a sodium restricted diet on the blood pressure level (3) and the difference in the rate of urinary excretion of salt and water in the hypertensive subject as compared to the normal (4) also point to some fundamental deviation from normal in the salt and water metabolism of the hypertensive subject. Because of the importance of this problem to a better understanding of the basic mechanisms underlying hypertensive cardiovascular disease, the present study was undertaken to compare the extracellular fluid volume in experimental and human hypertension with that of the normal. MATERIALS AND METHODSThe extracellular fluid volume was determined in a series of dogs rendered hypertensive by the application of a figure-of-eight ligature to the right kidney and ablation of the left organ (5). At least six months had intervened between the operation and the time of the experiments to permit the establishment of a stabilized blood pressure. Determinations were made simultaneously on a group of normotensive animals. Because of the uncertainty and difficulties attendant upon the determination of the extracellular volume, both mannitol and radioactive sulfate were utilized for this purpose. Although the use of inulin is considered to be the method of choice in man, erratic results are obtained when this substance is applied to the dog because of the large and variable blanks obtained in analysis of the blood under apparently constant conditions. The use of a constant infusion of mannitol (6) gave consistent and reproducible results. The radiosulfate method only was used in the experiments on the human.LAided by a grant from the Vaughn Fund. (7) with minor modifications. The animals were fasted for 12 to 14 hours prior to the determination but were allowed access to water at all times. They were trained to lie quietly on the animal board during the course of the procedure with only slight restraint.For the determination of extracellular volume by radiosulfate,2 carrier-free S' in the form of H,SO was used in doses of 100 microcuries as described elsewhere (8).