Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the post-absorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 hours before and 4 hours after an intravenous endotoxin injection (4 ng/kg body weight). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (p=0.001) and of glutamine by 25% (p=0.004) the third hour after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (p=0.05) and 9% (p=0.09) respectively. In parallel, the efflux from the leg increased by 35% (p=0.004) for the total sum of amino acids and by 43% (p=0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased.