The mechanism governing short-term adaptation to dietary protein restriction was investigated in nine normal adults by measuring their metabolic response to a standard mixed meal, first while they were adapted to a conventional, high-protein diet (day 1) and then again after they had eaten two low-protein meals (day 2). Urea appearance (measured as the sum of its urinary excretion and the change in body urea pool size), body retention of 15N-alanine included in each test meal, and whole-body protein turnover were calculated over the 9 hours following meal consumption on each day. Postprandial urea nitrogen appearance was 5.05 +/- 0.26 g/9 h on day 1 and decreased to 4.16 +/- 0.31 on day 2 (P < .05). Whole-body N flux (Q), protein synthesis (S), and protein breakdown (B) all decreased significantly on day 2 as assessed using either urea or ammonium end-product enrichments; however, recovery of 15N in the test meal as 15N-urea was similar on both days, approximately 22%. It is concluded that short-term metabolic adaptation occurs within two meals of reduced protein intake. The mechanism appears not to involve selectively an increased "first-pass" retention of dietary amino acids, but rather a general reduction in fed-state whole-body protein breakdown.