The deficient diuretic response to water which is characteristic of patients with adrenal insufficiency can be rapidly corrected by the administration of cortisone (1-3). The mechanism of the defective diuresis and the precise nature of the response to hormonal replacement have not been established. A number of observations, chiefly in experimental animals, have suggested that administration of various adrenocortical preparations in large "pharmacologic" doses also influences water diuresis in the normal organism (4). However, no systematic study of the latter effect has been made in man. The present report describes the effects of large doses of cortisone and hydrocortisone on water diuresis, renal solute excretion, glomerular filtration rate, and effective renal plasma flow in man. Striking augmentation of the maximal rates of urine flow observed during maintained water loading was a regular occurrence. The steroids studied appear to have a specific influence upon water reabsorption by the renal tubules, an action which can be separated from their effect on renal hemodynamics. MATERIALS AND METHODSThe subjects were adult male patients free from cardiovascular, renal and endocrine disease. Three sets of studies concerning water diuresis were carried out.Group I-A-Intermittent studies during prolonged intramuscular administration of cortisone. In these experiments creatinine clearance was measured, but not inulin or para-aminohippurate clearances. Urinary total solute concentration was calculated from determined cations and urea; freezing point determinations were not made.1 Present address: Veterans Administration Hospital, Syracuse, New York.Group I-B--Serial studies at intervals of one to three days during prolonged oral cortisone and hydrocortisone administration. Clearances of inulin and para-aminohippurate, as well as of creatinine, were determined. Urinary osmolality was measured cryoscopically.Group II-The acute response to intravenous infusion of hydrocortisone during water diuresis. Renal clearances and urinary total solute concentrations were measured as in I-B.Details of experimental procedure will be given together with the results in each group. Chemical methods and calculationsUrine and serum were analyzed for sodium, potassium, chloride and creatinine by methods previously described (5). Serum creatinine was determined after adsorption on Lloyd's reagent (6). Total solute concentration in urine and serum was measured by freezing point depression using a Fiske osmometer (Advanced Instruments, Inc., Needham, Mass.

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