During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.