Accelerated proteolysis of muscle is characteristic in patients with trauma or sepsis, but its cause is not well understood. Using rat muscle in vitro, we developed a bioassay to compare the proteolytic activity of plasma from 50 patients with trauma or sepsis with that of plasma from 14 normal volunteers and from 15 patients who had undergone "clean" elective surgical procedures. The mean proteolytic activity in the plasma of patients with trauma or sepsis was found to be 190 +/- 8.0 per cent of the control value (rat muscle incubated in medium alone), whereas the activity in normal plasma was 124 +/- 4.5 per cent (P less than 0.001). The activity in the plasma of patients who had undergone elective surgery was slightly elevated at 142 +/- 2.5 per cent (P less than 0.005). In 25 of the patients with trauma or sepsis the rate of amino acid release from one leg was measured by subtracting the concentration of tyrosine plus phenylalanine in the femoral artery plasma from that in the femoral vein; this rate correlated well with the bioactivity of the plasma in the bioassay system (r = 0.67, P less than 0.001). By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons.

Summary. Trichloroacetic acid extracts of plasma were fractionated on a CG-50 resin column and the 50% acetic acid eluents chromatographed on silicic acid-impregnated glass paper in butanol-acetic acid-water. The specific arginine vasopressin (AVP) zone was eluted and assayed for antidiuretic activity in the diuretic rat. Thioglycolate inactivation was used to confirm AVP activity. Recovery of as little as 4 FLU AVP per ml plasma ranged between 80 and 90%. In normal subjects after an overnight fast, plasma AVP ranged between 2.5 and 10.0 ,U per ml. AVP secretion was inhibited by hemodilution and stimulated with nicotine and hypertonic saline. Plasma AVP was absent in patients with diabetes insipidus even after neurohypophyseal stimulation. Plasma AVP was abnormally elevated during mild dehydration and remained above the normal range despite hemodilution in patients with untreated adrenocortical insufficiency demonstrating a delayed water diuresis. Glucosteroid therapy lowered plasma AVP to normal in dehydrated patients. A normal diuretic response to hydration was accompanied by a fall in plasma AVP to zero in steroid-treated patients. These findings suggest that hypersecretion of AVP may play an important role in the abnormal water metabolism of adrenocortical insufficiency and that the glucosteroids promote normal water diuresis by inhibiting the secretion of AVP from the neurohypophysis. IntroductionIncreased or sustained antidiuretic hormone (ADH) secretion has long been implicated in the abnormal water metabolism of primary and secondary adrenocortical insufficiency. The gluco-

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