Patients with congestive heart failure have been considered to have augmented sympathetic drive both at rest and during dynamic exercise. The augmentation observed during exercise may be related to the state of near exhaustion experienced by patients with heart failure at relatively low work loads. To compare the response of the sympathetic nervous system to exercise in normal subjects and patients with heart failure when they are working in a comparable physiologic frame of reference, the data for both groups can be expressed as percent peak oxygen consumption achieved (percent peak VO2) rather than as a function of absolute oxygen consumption (VO2). Ten healthy control subjects and 31 patients with chronic clinical class II and III heart failure were studied during upright maximal bicycle exercise. Eighteen of the 31 patients had primary cardiomyopathy and 13 had ischemic cardiomyopathy. The average ejection fraction at rest was 24 ± 10% (±SD) in the group with heart failure. Heart rate, systolic blood pressure, VO2 and plasma norepinephrine levels were measured at rest and throughout exercise. When the data were expressed as a function of percent peak VO2 achieved, patients with heart failure demonstrated a flatter slope (p = 0.004) than normal in the response of plasma norepinephrine to exercise, indicating a relative blunting of sympathetic drive. This was accompanied by attenuated heart rate (p = 0.001) and blood pressure (p < 0.001) responses. These differences were not apparent when the data are expressed as a function of absolute VO2. Thus, patients with heart failure may have a relative attenuation rather than augmentation of sympathetic drive during exercise when comparisons are made using a comparable physiologic frame of reference. Reduced sympathetic drive might partially explain the blunted heart rate and blood pressure responses to exercise and is consistent with the broader hypothesis that heart failure is characterized by a generalized inability of various stimuli to maximally activate the sympathetic nervous system despite increased sympathetic drive in the basal state.