Patients with heart failure frequently exhibit an excessive ventilatory response to exercise, which is acutely unaltered by therapeutic interventions. To investigate whether these ventilatory responses resolve after cardiac transplantation, 15 ambulatory patients with severe heart failure underwent exercise testing with measurement of respiratory gases before and 1.4 +/- 0.6 months after transplantation. Ventilatory response was also measured in 7 age-matched, sedentary control subjects. Left ventricular ejection fraction at rest and hemodynamic measurements were obtained before and after transplantation in all patients. After transplantation, ejection fraction at rest increased from 16 +/- 6 to 56 +/- 10%, pulmonary capillary wedge pressure declined from 26 +/- 8 to 12 +/- 5 mm Hg, and cardiac index increased from 1.7 +/- 0.5 to 2.8 +/- 0.5 liters/min/m2 (all p < 0.001). Peak oxygen consumption increased from 11.8 +/- 1.9 to 19.2 +/- 3.1 ml/kg/min (p < 0.001), but remained significantly lower than that in control subjects (33.4 +/- 6.9 ml/kg/min; p < 0.01). Minute ventilation (V(E)) was significantly reduced after transplantation, but excessive compared with normal values. Ventilation at a carbon dioxide production of 1 liter/min decreased significantly after cardiac transplantation (52.1 +/- 7.9 to 38.8 +/- 3.8 liters; p < 0.01), but remained elevated when contrasted to that in control subjects (31.4 +/- 3.4 liters; p < 0.05). Ventilatory response to exercise is significantly improved after cardiac transplantation; however, V(E) remains excessive. This may reflect an attenuated cardiac output response to exercise, abnormal intrapulmonary pressures or persistent deconditioning.