Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1-13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.