Carnitine is an indispensable factor for the beta-oxidation of medium- and long-chain fatty acids, and it plays a possible role in the oxidation of branched-chain amino acids. Plasma and urinary levels of free carnitine and short-chain acyl-carnitines were studied in 67 surgical patients, after non-septic surgical procedures or during sepsis. The septic state was associated with increased urinary excretion of free carnitine (p less than 0.001), as well as with lower plasma levels of short-chain acyl-carnitines (p less than 0.001); the latter feature correlated with the level of hypermetabolism, as evaluated by the metabolic rate and by the arterial-mixed venous O2 difference. In 26 patients during total parenteral nutrition D, L-acetyl-carnitine was administered (100 mg/kg/24 hrs, in continuous iv infusion) and was associated, in septic patients only, with a significant decrease in the respiratory quotient, suggesting enhanced oxidation of low respiratory quotient substrates (fatty acids and/or branched-chain amino acids). Carnitine supplementation during total parenteral nutrition might be of theoretical benefit in some clinical conditions, such as sepsis, in which the following conditions coexist enhanced utilization of substrates whose oxidation is partially or totally carnitine dependent; prolonged absence of exogenous intake of carnitine (as in long-term total parenteral nutrition); eventual impairment of carnitine synthesis due to hepatic dysfunction; increased, massive urinary loss of carnitine.