Our attempts to gain information concerning the amount of electrolyte in cell water and the theoretical concentration of intracellular cations necessarily revolve around our ability to partition total body water into extracellular and intracellular phases. The total body potassium, for example, is confined almost exclusively to the intracellular phase, and if the intracellular volume of the body could be defined, the net intracellular potassium concentration could be readily calculated as:Total body K -Extracellular K Intracellular fluid volume The most rational interpretation of extracellular fluid volume would seem to be that defined originally by Manery, Danielson, and Hastings (1), by Manery and Hastings (2) and later by Nichols, Nichols, Weil, and Wallace (3). These authors divide the extracellular fluid into the following components: the plasma water, the interstitial water, and the connective tissue water. The interstitial water is considered that volume of fluid which rapidly equilibrates with substances such as inulin. Connective tissue water is the volume of water which is principally associated with collagen and elastin, and with which substances such as inulin equilibrate slowly. The study of Nichols, Nichols, Weil, and Wallace (3) would indicate that the sum of these three phases of the extracellular fluid is defined reasonably well by the chloride space if correction of the chloride space is made for intracellular chloride, and for the slightly greater concentration of chloride in connective tissue water than is present in an ultrafiltrate of serum.The major aim of the present study is to test 1 This investigation was supported in part by a research grant (H-1638) from the National Heart Institute, National Institutes of Health, United States Public Health Service.further the validity of the chloride space, corrected for the factors described above, as a measure of the extracellular volume by demonstrating an identity between it and the space calculated from the sodium content of extracellular fluid. Extracellular fluid volume has been calculated from sodium by the expression (extracellular sodium)/(Na)ef where extracellular sodium is the difference between total body sodium and the sodium which is not in the extracellular fluid (i.e., that in bone, cells, and within the lumen of the gastrointestinal tract) and (Na)ef is the sodium concentration of the serum ultrafiltrate.Values for total body chloride and sodium on which the calculations depend have been obtained by carcass analysis of a large number of normal rats (4,5). Values for bone sodium have been calculated from the Na/Ca ratio for bone and from total body calcium. Values for cell sodium in muscle have been taken from data in the literature (6) calculated on the assumption that chloride in muscle occupies the same space as inulin and an exclusively extracellular position (7). Values for sodium in red cells were also calculated from the data of other investigators (8, 9) while those in visceral cells have been assessed by comparison of the ...