Metabolic changes induced in the rat by food restriction were assessed by administration of insulin (0.025 U/kg BW). The animals subjected to a 2 hr feeding/22 hr fasting schedule during one week have a greater capacity to recover from hypoglycemia even after 4 and 8 hr of fasting, whereas those with free access to food have a far lesser capacity to recover. Food restriction also caused a greater resistance to hepatic glycogen depletion during the hypoglycemic phase. It is likely that the metabolic adaptation during food restriction is important for glucose homeostasis and for rapid mobilization of energetic substrate during prolonged fasting.