1. Whole body protein turnover was measured using a primed-constant infusion of L-[1 −13 C]leucine with measurement of breath 13 CO 2 production and plasma 13 C α-ketoisocaproate enrichment. Ten fasting patients, requiring mechanical ventilation and suffering from multiple organ failure, and six healthy control subjects were studied. 2. Protein breakdown and leucine removal from the plasma for protein synthesis were significantly higher in the patients than in the control subjects ( P <0.01). In addition, leucine oxidation was almost 75% higher in the patients than in the healthy control subjects ( P <0.05). 3. Plasma concentrations of glucose, insulin and growth hormone were not different between the two groups, but those of glucagon (not significant), noradrenaline ( P <0.05) and cortisol ( P <0.01) were almost two- and three-fold higher in the patients than in the control subjects. 4. Mean energy expenditure, measured by indirect calorimetry, was 30% higher in the patients than in the healthy control subjects ( P <0.01). 5. Combining the data from both groups of subjects and using multiple regression analysis, cortisol was found to be the most significant predictor of (i) protein breakdown (48% of variance explained), (ii) leucine oxidation (69%) and (iii) hourly energy expenditure (54%). 6. The present investigation using [ 13 C]leucine tracer methods demonstrated, in patients with multiple organ failure, that whole body protein breakdown and synthesis increased concomitantly and were twice as high as rates measured in healthy control subjects. Of the hormones measured in the present study, Cortisol appears to have the most significant effect on whole body protein turnover.