Exercise is associated with a marked increase in glucose uptake by muscle, which is initially supported by breakdown of hepatic glycogen and subsequently by increased gluconeogenesis. If hepatic glucose production is inadequate, hypoglycemia results. During exercise there is decreased plasma insulin and increased catecholamines, glucagon, cortisol, and growth hormone, which contribute to but are not essential for the increased hepatic output of glucose. Although insulin concentrations fall, insulin sensitivity is increased. However, the augmented glucose uptake by muscle is due to other factors. The symptoms of exhaustion during exercise are not due to hypoglycemia, and prevention of hypoglycemia may not prolong the time of exercise to exhaustion. During severe caloric restriction, hepatic glucose production decreases and free fatty acids and ketone bodies become important sources of calories. Although under these circumstances hepatic gluconeogenesis is usually sufficient to prevent hypoglycemia, with very severe caloric restriction hypoglycemia can result. With starvation, insulin concentrations fall while growth hormone and glucagon increase. Frequently the usual symptoms of hypoglycemia are absent in individuals with hypoglycemia from severe caloric restriction. Hypoglycemia from severe caloric restriction has not been totally restricted to underdeveloped areas of the world. In such patients no endocrine abnormalities have been found, and hypoglycemia has persisted despite administration of large amounts of carbohydrate. Pregnancy and lactation could predispose to hypoglycemia in the face of inadequate caloric intake.