Context: Skeletal muscle protein synthesis is highly responsive to food intake. It has been suggested that the postprandial increase in circulating insulin modulates the muscle protein synthetic response to feeding. Objective: The objective of the study was to investigate whether a greater postprandial rise in circulating insulin level increases amino acid uptake in muscle and augments postprandial muscle protein synthesis rates. Participants and Design: Forty-eight healthy young (age 22 +/- 1 y; body mass index 22.0 +/- 0.3 kg/m(2)) and older males (age 68 +/- 1 y; body mass index 26.3 +/- 0.4 kg/m(2)) ingested 20 g intrinsically L-[1-C-13]-leucine-and L-[1-C-13]-phenylalanine-labeled casein protein with or without local insulin infusion. Primed continuous infusions of L-[1-C-13]-leucine and L-[ring-H-2(5)]-phenylalanine were applied, with arterial and venous blood samples and muscle biopsies being collected during a 5-hour postprandial period. Results: Insulin administration did not increase overall leg blood flow (P =.509) but increased amino acid uptake over the leg in both young and older subjects (P =.003). The greater amino acid uptake over the leg did not further increase postprandial muscle protein synthesis rates (0.050%+/- 0.006% and 0.037%+/- 0.004% per hour vs 0.044%+/- 0.004% and 0.037%+/- 0.002% per hour in the insulin-stimulated vs control condition in the young and older groups, respectively; P =.804) and did not affect postprandial deposition of dietary protein-derived amino acids in de novo muscle protein (P =.872). Conclusion: Greater postprandial plasma insulin availability stimulates amino acid uptake overthe leg but does not further augment postprandial muscle protein synthesis rates or stimulate the postprandial deposition of protein derived amino acids into de novo muscle protein in healthy young and older men.