AROGYASAMI, J., H. T. YANG, and W. W. WINDER. Effect of caffeine on glycogenolysis during exercise in endurance trained rats.Med. Sci. Sports Exerc, Vol. 21, No. 2, pp. 173–177, 1989. Caffeine has been reported to enhance performance by increasing lipid oxidation and sparing liver and muscle glycogen in human subjects during prolonged endurance exercise. In the present study, the effects of intravenous caffeine on the liver and muscle glycogenolysis during exercise in endurance trained rats were investigated. Male endurance trained rats (2 h·d-1for 6–7 wk) were given injections of 5 mg·kg-1caffeine (5 CAF), 25 mg·kg-1caffeine (25 CAF), or 0.9% sodium chloride (SAL) and were run on the treadmill for 45 min, 90 min, or until exhaustion at 26 m·min-1up a 15% grade. Intravenous caffeine did not enhance the endurance run time: 5 CAF = 149 ± 14 min, 25 CAF = 152 ± 10 min, and SAL = 176 ± 10 min. Caffeine did not influence the rate of liver glycogenolysis during exercise [liver glycogen (mmol glucose units·g-1) after 90 min: 5 CAF = 139 ± 26, 25 CAF = 133 ± 25, and SAL = 120 ± 32]. Liver cAMP, muscle glycogen, plasma free fatty acids, blood glucose, and lactate were likewise not affected by caffeine [plasma free fatty acids (mM) after 90 min: 5 CAF = 0.42 ± 0.04, 25 CAF = 0.45 ± 0.07, and SAL = 0.41 ± 0.05]. These data indicate that intravenous caffeine does not enhance the endurance run time or alter the plasma free fatty acids or liver and muscle glycogen utilization in endurance trained rats.