The pulmonary artery pressure response to exercise has been used as an index of cardiac reserve and frequently mirrors diastolic conditions. To define this response after orthotopic heart transplantation, we exercised 27 subjects on supine bicycle ergonometers. Stroke volume and pulmonary artery pressure were monitored with contrast-enhanced Doppler imaging. Study patients had undergone orthotopic heart transplantation. Seventeen patients were screened, and eight were subsequently determined by endomyocardial biopsy to be histologically free of acute cardiac allograft rejection. A control population of nonconditioned normal volunteers was also evaluated (heart transplant patients: n = 8, age = 45.7 +/- 7.3 years, seven men; normals volunteers: n = 10, age = 49.4 +/- 12.8 years, nine men; P = NS). Total exercise time and peak heart rate were reduced in heart transplant patients: 7.6 +/- 2.5 minutes, 123 +/- 4 beats/min versus normal volunteers: 16.2 +/- 4.5 minutes, 134 +/- 4 beats/min (P < 0.05). Change in stroke volume from baseline to peak exercise was greater in heart transplant patients: 29.9 +/- 4.6 ml versus normal volunteers: 3.9 +/- 5.7 ml (P < 0.01). No difference was observed in the pulmonary artery pressure response to exercise. In patients with uncomplicated heart transplantation a reduction in exercise capacity is shown; however, the pulmonary artery pressure response to exercise is comparable to normal subjects. A blunted heart rate response is observed, which is partially compensated by increases in stroke volume. These findings suggest that cardiac diastolic function is preserved and that denervation of the heart accounts for impaired exercise tolerance.