BACKGROUND: Little is known about the autonomic control of the native sinus node (NSN) after heart transplantation because its electrical activity is difficult to detect with skin electrodes. METHODS AND RESULTS: The intracardiac electrogram of the NSN and the donor heart electrocardiogram were measured simultaneously. A total of 351 recordings of 107 heart transplant patients (age 53.6+/-12.3 years) were obtained up to 1 year after transplantation. In a subgroup of 41 patients, consecutive recordings were made. Eleven recordings of heart failure patients (age 56.2+/-6.5 years) awaiting cardiac transplantation were used as controls. To examine a relationship between autonomic indices of the NSN and hemodynamics of the donor heart, intracardiac pressures and cardiac output were recorded in the same session. Heart rate variability (HRV) parameters in time and frequency domain of the NSN showed a significant increase starting at 6 months after transplantation, whereas heart rate of the NSN tended to decrease. Heart rate and HRV parameters remained constant over the first year in the donor heart. Higher values of low-frequency and high-frequency powers in the NSN were associated with lower values of right ventricular, pulmonary artery, and mean atrial pressure and cardiac output. Recordings of patients with rejection could not be distinguished from those without rejection based on the spectral content of HRV of either the NSN or the donor heart. CONCLUSIONS: These data suggest a restoration of autonomic modulation of the NSN. This restoration is associated with hemodynamic improvement of the donor heart.