Brain-dead organ donors are depleted of circulating triiodothyronine (T3) and show features suggestive generally of anerobic metabolism at the tissue level, accompanied by deteriorating hemodynamic function. The principle of single-bolus kinetics with labeled carbon compounds (14C-R), with subsequent measurement of both plasma activity and of exhaled14C 02 has therefore been used to study glucose, pyruvate, and palmitate utilization under conditions of (1) sedation, (2) brain death, and (3) brain death with T3 therapy in the baboon. Serum lactate and plasma-free fatty acid concentrations were also measured. There was a major change in metabolic oxidative processes following brain death. The rate of glucose, pyruvate, and palmitate utilization was markedly reduced, and there was an accumulation of lactate and free fatty acids in the plasma, indicating a general change from aerobic to anerobic metabolism. The administration of T3 to the brain-dead baboon resulted in a dramatic increase in the rate of metabolite utilization, and a reduction in the plasma concentrations of plasma lactate and free fatty acids, indicating an apparent reversal from tissue anaerobic to aerobic metabolism. We suggest that T3 should be administered to all brain-dead potential organ donors to correct and maintain a more physiologic metabolic status and thus to improve organ function. © 1988 by The Williams & Wilkins Co.