Isotonic glucose is often the sole nutrient provided to hospitalized patients with varying degrees of protein calorie malnutrition. To study the effects of such diets uncomplicated by illness, normal human subjects were fasted (6 to 14 days) before receiving an infusion of 5% dextrose (5 to 7 days). Norepinephrine excretion rose steadily-to six times control values-during the first 6 days of the fast and changed little thereafter. It remained high during the first 3 days of glucose infusion and subsequently returned toward normal. The rate of NTau-methylhistidine excretion changed little during the fast but decreased abruptly with glucose infusion. The magnitude of NTau-methylhistidine excretion indicated that undirectional muscle protein degradation was about equal to nitrogen excretion during the fast, and that the decrease in muscle protein degradation could account for the abrupt decrease in nitrogen excretion (from 91 to 30 mg N/kg . day) after glucose infusion. This suggests that the conservation of muscle protein caused by glucose infusion in this setting is affected by decreased degradation rather than by increased synthesis. Changes in NTau-methylhistidine excretion and total nitrogen excretion were more rapid than, and therefore not mediated by, changes in insulin concentration or norepinephrine excretion.