Adaptations of leucine and glucose metabolism to 3 d of fasting were examined in six healthy young men by use of L-[1-13C]leucine and D[6,6-2H2]glucose as tracers. Leucine flux increased 31% and leucine oxidation increased 46% after 3 d of fasting compared with leucine flux and oxidation after an overnight fast. Glucose production rate declined 38% and resting metabolic rate decreased 8% during fasting. Plasma concentrations of testosterone, insulin, and triiodothyronine were reduced by fasting whereas plasma glucagon concentrations were increased. We conclude that there is increased proteolysis and oxidation of leucine on short-term fasting even though glucose production and energy expenditure decreased.