Fasting energy metabolism was studied in infants to determine the rates of utilization of endogenous carbohydrate, fat, and protein in relation to length of fasting, glucose homeostasis, other circulating energy substrates and hormones, and severe depletion of energy reserves due to prior malnutrition. Five subjects about 1 yr of age were each studied before and after restoration of their energy reserves. Following 3 days of a standard maintenance intake of energy and protein, the subjects were fasted until glycogen oxidation became negligible. Total energy utilization, determined by hourly oxygen consumption, did not diminish as a result of fasting but was significantly less when malnourished than when recovered, 66 versus 79 kcal/kg/day. In all cases the major energy source shifted from oxidation of dietary carbohydrate and glycogen to oxidation of fat, determined from the respiratory quotient, until the oxidation of glycogen became negligible and fat provided 94% of energy in the malnourished subjects after 21 hr and 92% in the recovered subjects after 27 hr. Utilization of protein, determined from urinary nitrogen excretion, remained very low in the malnourished infants accounting for a maximum of 4% of energy, 103 mg N/kg/day, whereas after recovery, protein utilization doubled as a result of fasting, finally accounting for 7% of energy, 226 mg N/kg/day (p less than 0.005). Urea accounted for 60% of total urinary N in both groups and plasma urea increased correspondingly in the recovered but not in the malnourished subjects. Plasma glucose decreased to about 40 mg/100 ml in both groups as glycogen oxidation diminished. The maximum amount of glucose that could have been derived from dietary carbohydrate, glycogen, glycerol, and amino acids decreased over this time from about 6 to 1 mg/kg/min. Alanine declined in relation to glucose concentration and was not different in the two groups in spite of the difference in urea production. Glycerol free fatty acids, beta-hydroxybutyrate, and acetoacetate increased in both groups, but the latter three of these remained significantly less in the malnourished group. Insulin decreased rapidly and remained equally low in both groups. Urinary epinephrine increased in both groups and cortisol was elevated after fasting, while growth hormone did not increase significantly. It is concluded that fasting infants complete the transition from dietary carbohydrate to endogenous fat as the major energy source much faster than do adults, proportionate to relatively greater energy utilization. Severe wasting did not prevent energy homeostasis in spite of greatly depleted body fat. Oxidation of fat continued to provide virtually all of the fasting energy requirements, although ketosis was relatively less. Utilization of endogenous protein also increased as a result of fasting but, by contrast, provided only a very small fraction of total energy, and this was substantially diminished as a result of wasting, similar to what has been found in starved adults...