Hepatic glucose production increases during exercise as a sum of liver glycogenolysis and gluconeogenesis. Whereas the former dominates during intense exercise, the latter contributes substantially with prolonged exercise and the concomitant decline in liver glycogen stores and with increased gluconeogenic precursor supply. Afferent neural feedback signals from contracting muscle and feedback signals mediated via the blood stream, can stimulate glucose production to maintain euglycemia. A rise in blood glucose directly inhibits hepatic glucose production, whereas a decline in blood glucose enhances liver glucose production via release of glucoregulatory hormones. In addition to this, central mechanisms coupled to the degree of motor center activity can be responsible for part of the increase in glucose mobilization, especially during intense exercise where hepatic glucose release exceeds peripheral glucose uptake and plasma glucose rises. A decline in plasma insulin is important for the rise in glucose production during exercise in a variety of species, whereas an increase in plasma glucagon is probably more important in other species than man, where glucagon plays a role only in prolonged exercise. Sympathetic nervous activity to the liver and circulating norepinephrine has been demonstrated to be without any role in glucose production, whereas epinephrine has a minor stimulating effect on hepatic glucose mobilization during intense exercise. Growth hormone and cortisol contribute only minimally to the exercise induced rise in liver glucose output.