The participation of hepatic glycogenolysis and gluconeogenesis to the glycemic changes promoted by exercise was investigated. For this purpose, we employed swimming rats (2.5% body weight extra load attached to the tail, at 24 degrees C) using a favorable condition to measure hepatic glycogenolysis (fed rats) and a favorable condition to measure hepatic gluconeogenesis (fasted rats). This experimental approach permits us to compare the contribution of hepatic glycogenolysis and gluconeogenesis to glucose changes for a specific schedule of exercise. The animals were investigated at rest, after 5 minutes of swimming and after swimming to exhaustion. Our results show that hepatic glycogen has a crucial role to determine hyperglycemia during exercise. In contrast, hypoglycemia developed during exercise when glycogen was depleted. However, the ability of the liver to produce glucose from L-lactate, glycerol and L-glutamine was increased during exercise. Taken together, these findings suggest that the hepatic capacity to produce glucose from gluconeogenic substrates (except for L-alanine) was increased when hepatic glycogen stores were depleted. Thus, the increased capacity to produce glucose shown by livers from exercising rats must to be an important metabolic adaptation to protect against severe hypoglycemia.