The effect of insulin and leucine on amino acid and protein metabolism in muscle is not fully understood. To characterize their separate and combined effects on free amino acids in muscle and plasma, 11 volunteers received an infusion of either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed by a combination of the two infusions for an additional 2-h period. In muscle both the leucine infusion and the leucine plus glucose infusion increased the concentration of free leucine significantly, while the sum of the other branched chain amino acids (BCAA), of the aromatic amino acids and of the basic amino acids decreased. Glucose infusion alone decreased the sum of the essential amino acids, the BCAA and the aromatic amino acids. The combination of leucine and glucose augmented the decreases, while the concentrations of glutamate, glutamine and alanine were unaffected. In plasma the leucine infusion doubled the leucine concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine and the sum of the aromatic amino acids. Glucose infusion decreased methionine, serine, isoleucine and the sum of the essential amino acids and of the BCAA. The combination of leucine infusion and hyperinsulinaemia augmented the decreases. The plasma concentrations of the keto acids of valine and isoleucine decreased by the leucine infusion while the concentrations of the keto acid of leucine and isoleucine decreased by glucose infusion. The combination of leucine and glucose had an additive effect. These effects are attributed to a specific effect of leucine on the other two BCAA and a depression of muscle proteolysis by both leucine and insulin, resulting from glucose infusion.