The postprandial retention of dietary protein decreases when the prevailing protein intake increases. We investigated the influence of the prevailing protein intake on the regional utilization and anabolic use of wheat protein during the postprandial non-steady state in humans. Healthy adults (n ҃ 8) were adapted for 7 d, first to a normal-protein diet (NP: 1 g ⅐ kg Ҁ1 ⅐ d Ҁ1) and then to a high-protein diet (HP: 2 g ⅐ kg Ҁ1 ⅐ d Ҁ1). After each adaptation period, the subjects received the same single, solid mixed meal containing [ 15 N]-labeled wheat protein. The postprandial kinetics of dietary nitrogen were then measured for 8 h in blood and urine. These data were further analyzed by using a multicompartmental model to predict the postprandial kinetics of dietary nitrogen in unsampled pools. The postprandial whole-body retention of wheat protein nitrogen, measured 8 h after meal ingestion, decreased by 10% when the subjects switched from the NP diet to the HP diet. According to modeling results, this resulted from an increased splanchnic utilization of dietary nitrogen for urea production, whereas its incorporation into splanchnic proteins was unchanged, leading to a 20-30% decrease in peripheral availability and anabolic use in HP-adapted compared with NP-adapted subjects having ingested the same protein load. By combining clinical experimentation with compartmental modeling, we provide a global overview of postprandial dietary protein metabolism. Increasing prior protein intake was shown to reduce the postprandial retention of wheat protein nitrogen, mainly by diminishing the efficiency of its peripheral availability and anabolic use.