The purpose of this investigation was to determine whether atrial natriuretic peptide (ANP) secretory function is preserved after cardiac transplantation. Thirteen hemodynamically stable outpatients performed supine exercise on a bicycle an average of 7 months after orthotopic cardiac transplantation. Right atrial pressure increased 2.2-fold (6 +/- 1 to 13 +/- 2 mm Hg) and pulmonary artery wedge pressure 2.1-fold (11 +/- 1 to 23 +/- 7 mm Hg) with exercise in the transplant recipients. Resting venous ANP level (114 +/- 19 pg/ml) and peak exercise venous level (373 +/- 61 pg/ml) was elevated in transplant recipients (p less than 0.001) compared with control subjects (21 +/- 1 and 92 +/- 14 pg/ml, respectively. This represents a 3.3-fold (114 +/- 19 to 373 +/- 61 pg/ml) increase in the ANP level from resting to exercise in transplant recipients and a 4.4-fold (21 +/- 1 to 92 +/- 14 pg/ml) increase in control subjects. A correlation between venous ANP levels and hemodynamics (right atrial pressure) was observed r = 0.49 p = 0.01. It is concluded that ANP levels at rest are elevated after cardiac transplant, the levels correlate with the intracardiac hemodynamics, and exercise-induced augmentation of plasma levels occurs.