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Many patients with edema of congestive cardiac failure, nephrosis, and cirrhosis become refractory to all diuretic therapy. Theoretically, the use ia adequate dosage of osmotic diuretics whose action is dependent upon physical factors should augment sodium, chloride, and water excretion from whatever level exists prior to their use. In refractory edema, the effect of other diuretics (via alteration of the imetabolie, actively resorbing mechanisms of the tubular cells) on tubular rejection of sodium, chloride, and water should be increased by osmotic diuretics. Mannitol was administered intravenously in large doses to test the effectiveness of osmotic diuretics in refractory edema.OSMOTIC diuretics exert their action through physical rather than cellular metabolic effects.'-3 Osmotic diuretic action depends upon the presence of nonabsorbable particles within the isosmotic proximal tubule.These nonabsorbable particles cause retention of water within the proximal tubule to maintain a constant total osmolar concentration of 310 mOsM. per Lj. As compared with the preosmotic diuretic baseline, the water that is so retained progressively dilutes the sodium in the fluid as it traverses the proximal tubule. Thus, an unchanged cell surface area containing the active metabolic sites for sodium resorption is exposed to a fluid of progressively lesser sodium concentration.' The absorbing sites being less saturated, less sodium particles are absorbed (despite unaltered avidity of the individual cell sites), and more sodium particles passed on distally. Within the proximal tubule the additional nonabsorbed sodium and accompanying anions behave as osmotic diuretic particles4 and retain water that also is passed on distally. In the distal convoluted tubule, absolute quantities absorbed, even when maximal, are small fractions of the increased total quantities presented and explain the inability of the distal tubule greatly to modify the nature of the fluid presented to it.1-3 Urine during such marked osmotic diuresis is similar to the fluid leaving the proximal tubule in total concentration, pH, and individual ion concentra-

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