AROGYASAMI, J., H. T. YANG, and W. W. WINDER. Effect of intravenous caffeine on muscle glycogenolysis in fasted exercising rats.Med. Sci. Sports Exerc, Vol. 21, No. 2, pp. 167–172, 1989. Caffeine has been reported to enhance performance by increasing fat utilization and by sparing liver and muscle glycogen. The lipolytic effect of caffeine has been reported to be diminished in response to previous carbohydrate loading of the subjects. The present study was designed to investigate the effects of caffeine during submaximal exercise in rats where the influence of dietary carbohydrate was removed by fasting. Rats were fasted overnight and given injection of 25 mg·kg-1caffeine (CAF) or 0.9% NaCl (SAL) 60 min before exercise. They were run for 15, 30, and 60 min on a rodent treadmill up a 15% grade at 21 m·min-1. Plasma free fatty acids (FFA) were significantly elevated to 0.72 ± 0.04 mMin CAF as compared to 0.45 ± 0.03 mMin SAL at the beginning of exercise. During exercise, however, a significant difference in FFA levels between CAF and SAL was seen only at 30 min and not at other time points. No significant decrease in muscle glycogenolysis was observed in the CAF as compared to SAL rats, and the liver cyclic AMP remained the same in both CAF and SAL. Blood lactate (mM) showed an increase due to caffeine only at 15 min of exercise (CAF = 2.4 ± 0.2; SAL = 1.7 ± 0.3). Intravenous caffeine during exercise did not alter plasma glucagon or blood glucose. We conclude that caffeine has no effect on muscle glycogen utilization in fasted rats during exercise even though there was an increased FFA in CAF rats at the beginning of exercise.