PURPOSE: Exercise increases the use of amino acids for glucose production and stimulates the oxidation of amino acids and other substrates to provide ATP for muscular contraction, and thus the availability of amino acids and energy for postexercise muscle protein synthesis may be limiting. The purpose of this study was to determine the potential of postexercise nutrient intake to enhance the recovery of whole-body and skeletal muscle protein homeostasis in humans. METHODS: Primed-continuous infusions of L-[1-13C]leucine and L-[ring-2H5]phenylalanine were initiated in the antecubital vein and blood was sampled from a femoral vein and a heated (arterialized) hand vein. Each study consisted of a 30-min basal, a 60-min exercise (bicycle at 60% VO2max), and a 180-min recovery period. Five men and five women were studied three times with an oral supplement administered immediately following exercise in random order: NO = 0, 0, 0; SUPP = 0, 8, 3; or SUPP+PRO = 10, 8, 3 g of protein, carbohydrate, and lipid, respectively. RESULTS: Compared to NO, SUPP did not alter leg or whole-body protein homeostasis during the recovery period. In contrast, SUPP+PRO increased plasma essential amino acids 33%, leg fractional extraction of phenylalanine 4-fold, leg uptake of glucose 3.5-fold, and leg and whole-body protein synthesis 6-fold and 15%, respectively. Whereas postexercise intake of either NO or SUPP resulted in a net leg release of essential amino acids and net loss of whole-body and leg protein, SUPP+PRO resulted in a net leg uptake of essential amino acids and net whole-body and leg protein gain. CONCLUSIONS: These findings suggest that the availability of amino acids is more important than the availability of energy for postexercise repair and synthesis of muscle proteins.