The mode of action of the hormone of the adrenal cortex necessary for life has been the subject of much discussion. Among the prominent hypotheses for explaining the symptoms of adrenal cortical insufficiency are loss of sodium and chloride with accompanying changes in the distribution of body water (1, 2, 3); toxic effects of potassium (4,5,6,7); disturbance in the distribution of body water not clearly related to loss of sodium or retention of potassium (8); and disturbances in metabolism or carbohydrate (9). Since it seems, at present, bootless to attempt to relate the anomalies in carbohydrate metabolism to the disturbances in metabolism of water and electrolyte, this aspect of the function of the adrenal cortex will not be discussed. The present investigation was undertaken to determine by tissue analyses the actual distribution of water and electrolyte in the tissues of adrenalectomized rats in relation to the toxic action of potassium and the therapeutic effect of sodium salts. EXPERIMENTAL PROCEDURE Healthy male albino rats weighing approximately 200 grams were adrenalectomized under ether anesthesia via the usual lumbar route. The majority of the animals were fed a low potassium diet of the following composition: lactalbumin 15 per cent, sucrose 25 per cent, dextrin 32 per cent, crisco 22 per cent, cod liver oil 1 per cent, yeast powder 2 per cent, bone ash 2 per cent and NaCl 1 per cent. One group of animals was fed a ration containing 1.5 grams of K,HPO, per 100 grams of the above diet. Diet 1 on analysis, was found to contain 0.03 per cent potassium whereas Diet 2 contained 0.7 per cent potassium. The animals were given distilled water, and the food and water intakes were measured daily.The adrenalectomized animals were divided into groups and treated as follows. The animals of the first group were sacrificed when symptoms of severe adrenal insufficiency were manifest. The time of onset of symptoms was exceedingly variable on Diet 1 so that the rats could not be sacrificed at stated intervals after operation if comparable results were to be obtained. Immediately after sacrificing the animals, the livers were removed and a sample of muscle was dissected off rapidly and freed of fat and connective tissue. The skin was removed in toto and the remainder of the carcass treated separately. All of the tissues were put into covered receptacles, weighed and then placed in an oven at 105°C. and dried until constant weight was attained.The dried tissues were ground to a powder in a small food chopper. The dried powdered tissues were kept in glass stoppered flasks and aliquots taken for analysis.One cubic centimeter samples of serum were accurately weighed in platinum dishes and the water content obtained by drying 24 hours in an oven at 1050 C. The dried residue was ashed in a furnace at 5000 C. for 2 hours.Serum chloride was determined by the method of Van Slyke and Sendroy (10). The tissue chloride was determined after ashing the material at 4500 C. in the presence of a large excess of sodium carbonate. Th...