BACKGROUND Exercise capacity after heart transplantation is abnormal. This reduced exercise performance may in part be due to treatment with high-dose immunosuppressive therapy, deconditioning, graft rejection, or cardiac denervation. METHODS To investigate whether exercise capacity significantly improves over time as immunosupression is lessened or whether reinnervation occurs, we measured peak exercise oxygen consumption in 60 patients 0.5 to 60 months after transplantation (age: 52 +/- 11 years; left ventricular ejection fraction: 56% +/- 10%) and in 14 healthy subjects (age: 44 +/- 8 years; p = Not significant). Resting hemodynamic measurements, left ventricular ejection fraction, and immunosuppressive therapy were recorded at the time of each of the patients' 116 exercise tests. Exercise test results were stratified into groups according to time after transplantation. RESULTS Exercise capacity significantly improved after transplantation (pretransplantation peak exercise oxygen consumption: 9.9 +/- 4.3; posttransplantation: 16.6 +/- 4.0 ml/kg/min; p < 0.001). Patient groups after transplantation were without significance differences with regard to age, gender, left ventricular ejection fraction, resting hemodynamic measurements, antihypertensive regimen, and number of rejection episodes. For those patients exercising at 2 months compared with the patients exercising at 12 months, a significant increase was observed in peak exercise oxygen consumption (14.0 +/- 3.8 ml/kg/min at 2 +/- 2 months to 16.2 +/- 3.8 ml/kg/min at 12 +/- 2 months) and maximum heart rate (124 +/- 24 to 137 +/- 24 beats/min). No significant changes were found in peak exercise oxygen consumption or maximum heart rate after the first year after transplantation. Patients' exercise capacities as measured by peak exercise oxygen consumption remained abnormal (N1 peak exercise oxygen consumption: 35 +/- 11 ml/kg/min) despite significant reductions in steroid, azathioprine, and cyclosporine therapy. Peak exercise oxygen consumption was significantly correlated with maximal heart rate (r = 0.42) (p < 0.0001) but not with maximal blood pressure response, change in heart rate, left ventricular ejection fraction, or resting cardiac index (all p = Not significant). CONCLUSIONS Exercise capacity is markedly improved after heart transplantation although it remains impaired compared with healthy individuals. Patients achieve their maximal exercise capacity by 1 year after transplantation. Subsequently, exercise capacity does not improve despite significant reductions in immunosuppressive agents. The lack of alteration in the heart rate response to exercise over time suggests that no significant functional reinnervation occurs.