In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover.