Purine nucleotide degradation is accelerated during strenuous exercise, and hypoxanthine (HX; p mol/L) increases in the plasma. In this study we determined purine degradation and sympathetic activation in subjects with varying degrees of exercise tolerance. Plasma HX (μmol/L), lactate (mmol/L), and norepinephrine (NE; ng/ml) were measured at cardiopulmonary exercise test in 41 controls,12 fit subjects, and 132 patients (NYHA 1: 47,11: 61,111: 24) with chronic heart failure (CHF). Peak VO2 decreased as CHF worsened (controls, Fit, CHF class I, II, III: 28.1±7.9,38.2±6.0,22.5±4.3,18.5±4.0,13.4 ±2.7 ml/min/kg, ANOVA p<0.0001). A Plasma HX (23.4±12.5,33.0±16.1,18.1±13.5,16.1 ± 8.9,9.6±3.7 p mol/L, ANOVA p<0.0001) and A blood lactate (5.1±2.0,6.7±1.8,4.2±1.7,3.8± 1.8,2.7 ±1.2 mmol/L, ANOVA p<0.0001)decreased according to the NYHA class. While A plasma NE was markedly higher only in fit subjects (2.19±1.61,5.25 ± 2.45,2.06±1.63,2.23±1.22,1.91 ± 1.02 ng/ml, ANOVA p<0.0001). In summary, purine degradation and lactate production were reduced as exercise capacity decreased, but exercise NE was markedly elevated in fit subjects. Thus, anaerobic markers decreased as heart failure worsened, suggesting that patients are unable to continue exercise in the anaerobic condition. Markedly elevated plasma NE in fit individuals suggests a potentially greater importance of high sympathetic activity for achieving a high level of exercise.