Plasma glucose is an important energy source in exercising humans, supplying between 20 and 50% of the total oxidative energy production and between 25 and 100% of the total carbohydrate oxidised during submaximal exercise. Plasma glucose utilisation increases with the intensity of exercise, due to an increase in glucose utilisation by each active muscle fibre, an increase in the number of active muscle fibres, or both. Plasma glucose utilisation also increases with the duration of exercise, thereby partially compensating for the progressive decrease in muscle glycogen concentration. When compared at the same absolute exercise intensity (i.e. the same VO2), reliance on plasma glucose is also greater during exercise performed with a small muscle mass, i.e. with the arms or just 1 leg. This may be due to differences in the relative exercise intensity (i.e. the %VO2peak), or due to differences between the arms and legs in their fitness for aerobic activity. The rate of plasma glucose utilisation is decreased when plasma free fatty acid or muscle glycogen concentrations are very high, effects which are probably mediated by increases in muscle glucose-6-phosphate concentration. However, glucose utilisation is also reduced during exercise following a low carbohydrate diet, despite the fact that muscle glycogen is also often lower. When exercise is performed at the same absolute intensity before and after endurance training, plasma glucose utilisation is lower in the trained state. During exercise performed at the same relative intensity, however, glucose utilisation may be lower, the same, or actually higher in trained than in untrained subjects, because of the greater absolute VO2 and demand for substrate in trained subjects during exercise at a given relative exercise intensity. Although both hyperglycaemia and hypoglycaemia may occur during exercise, plasma glucose concentration usually remains relatively constant. Factors which increase or decrease the reliance of peripheral tissues on plasma glucose during exercise are therefore generally accompanied by quantitatively similar increases or decreases in glucose production. These changes in total glucose production are mediated by changes in both hepatic glycogenolysis and hepatic gluconeogenesis. Glycogenolysis dominates under most conditions, and is greatest early in exercise, during high intensity exercise, or when dietary carbohydrate intake is high. The rate of gluconeogenesis is increased when exercise is prolonged, preceded by a restricted carbohydrate intake, or performed with the arms. Both glycogenolysis and gluconeogenesis appear to be decreased by endurance exercise training. These effects are due to changes in both the hormonal milieu and in the availability of hepatic glycogen and gluconeogenic precursors.(ABSTRACT TRUNCATED AT 400 WORDS)