BACKGROUND: Sarcopenia seems to be attributed to a blunted muscle protein synthetic response to food intake and exercise. This blunted response could be the result of impaired protein digestion and absorption kinetics and lead to lower postprandial plasma amino acid availability. OBJECTIVE: The objective was to compare in vivo dietary protein digestion and absorption kinetics and subsequent postprandial muscle protein synthesis rates at rest and after exercise between young and elderly men. DESIGN: Young and elderly men consumed a 20-g bolus of intrinsically l-[1-(13)C]phenylalanine-labeled protein at rest or after exercise. Continuous infusions with l-[ring-(2)H(5)]phenylalanine were applied, and blood and muscle samples were collected to assess in vivo protein digestion and absorption kinetics and subsequent postprandial muscle protein synthesis rates. RESULTS: Exogenous phenylalanine appearance rates expressed over time did not differ between groups. No differences were observed in plasma phenylalanine availability between the young (51 +/- 2%) and elderly (51 +/- 1%) men or between the rest (52 +/- 1%) and exercise (49 +/- 1%) conditions. Muscle protein synthesis rates calculated from the oral tracer were 0.0620 +/- 0.0065%/h and 0.0560 +/- 0.0039%/h for the rest condition and 0.0719 +/- 0.0057%/h and 0.0727 +/- 0.0040%/h for the exercise condition in young and elderly men, respectively (age effect: P = 0.62; exercise effect: P < 0.05; interaction of age and exercise: P = 0.52). CONCLUSIONS: Dietary protein digestion and absorption kinetics are not impaired after exercise or at an older age. Exercising before protein intake allows for a greater use of dietary protein-derived amino acids for de novo muscle protein synthesis in both young and elderly men. This trial was registered at clinicaltrials.gov as NCT00557388.