There is little information on the hemodynamic response to upright exercise in patients who have undergone cardiac transplantation. We compared the hemodynamic and metabolic response to upright bicycle exercise in 11 patients with heart transplants and 12 controls. Patients performed two tests--a steady-state test with a right heart catheter and a maximal incremental test. During steady-state exercise at 20% of their predicted maximum workload, patients with heart transplants had a higher (mean +/- SD, p < 0.05) heart rate (108 +/- 11 vs. 96 +/- 15 beats/min), mean systemic blood pressure (116 +/- 17 vs. 101 +/- 11 mmHg), mean pulmonary artery pressure (29 +/- 9 vs. 22 +/- 3 mmHg), mean pulmonary wedge pressure (14 +/- 6 vs. 9 +/- 2), pulmonary (302 +/- 101 vs. 220 +/- 50 d-sec-cm-5-m2) and systemic (2049 +/- 531 vs. 1459 +/- 520) resistance indices, and lactate concentration (3.4 +/- 1.7 vs. 1.7 +/- 0.4 mmol/l), and a lower stroke index (39 +/- 8 vs. 50 +/- 8 ml/m2) compared with controls. Cardiac index, right atrial pressure, and mixed venous oxygen saturation were similar. During the maximal exercise test, patients with heart transplants achieved a significantly lower percentage of predicted maximum heart rate (77 +/- 13 vs. 91 +/- 8%), workload (70 +/- 25 vs. 102 +/- 23%), oxygen consumption (63 +/- 11 vs. 108 +/- 19%), and ventilation (67 +/- 18 vs. 89 +/- 15%) compared with controls. Heart transplant patients also had a lower blood pressure and anaerobic threshold. We conclude that heart transplant patients have an altered hemodynamic and metabolic response to upright bicycle exercise.