Ten adult men were infused with L-[1-13C]leucine for 9 h commencing in the postabsorptive state (PA, 0-3 h), during the half-hourly feeding of low-protein meals (LP, protein = 2% calories, 3-6 h), and during feeding isoenergetic high-protein meals (HP, protein = 14% calories, 6-9 h). Leucine oxidation and turnover (protein synthesis and degradation) were determined from plasma alpha-[1-13C]ketoisocaproate enrichment and expired 13CO2 excretion measured during the third hour of each 3-h period. Plasma insulin increased markedly with feeding to a level that was maintained with both diets. The negative postabsorptive leucine balance became less negative during the LP meals (P < 0.01) and was positive with the HP meals (P < 0.01). The significant responses to feeding (all P < 0.01) were for oxidation -13% (PA-LP), +50% (LP-HP), and +29% (PA-HP); for degradation -24% (PA-LP), -30% (LP-HP), and -47% (PA-HP); and for synthesis -14% (PA-LP), +29% (LP-HP), and +11% (PA-HP). These data support a feeding mechanism involving both an insulin-mediated, protein-conserving influence of dietary energy that inhibits degradation, lowers amino acid levels, and reduces oxidation, and amino acid-mediated augmentation of the inhibition of degradation, a stimulation of synthesis, and an increase in oxidation when leucine dietary supply exceeds the capacity for its net deposition.