Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in patients with congestive heart failure (CHF). The aim of this study was to determine if the responses of atrial natriuretic peptide (ANP) normalized for peak oxygen consumption (peak VO2) to exercise are augmented in patients with CHF. Ventilatory and ANP responses were assessed in 28 patients with CHF (NYHA classes II: 16, III: 12), 17 patients in NYHA class I, and 14 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma ANP was measured at rest and immediately after peak exercise. The increase in ANP was divided by peak VO2 and this ratio [ANP-Exercise Ratio: (peak ANP-rest ANP)/peak VO2] was compared among the 3 groups. Peak VO2 (Normal, NYHA I, CHF: 29.9 +/- 1.7, 24.0 +/- 1.3, 17.4 +/- 0.8 ml/min per kg), anaerobic threshold and peak work rate were lower in patients with CHF. The resting ANP level was significantly higher in patients with CHF (Normal, NYHA I, CHF: 35.4 +/- 4.6, 42.9 +/- 5.8, 80.8 +/- 12.9 pg/ml). The ANP level increased during exercise in all 3 groups, and patients with CHF had a significantly higher ANP level than normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 65.3 +/- 10.7, 75.9 +/- 14.4, 141.6 +/- 20.1 pg/ml). The ANP-Exercise Ratio in patients with CHF was significantly higher than those in normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 0.96 +/- 0.26, 1.32 +/- 0.38, 3.59 +/- 0.72). These data suggest that patients with CHF but not those in NYHA class I have an augmented ANP response, as reflected by both absolute ANP levels and by the exercise ratio, which was normalized by the peak exercise level.