BACKGROUND: After heart transplantation, the donor heart is extrinsically denervated. No input of sympathetic or vagal nerves can influence the heart rate, resulting in a flat power spectrum of the beat-to-beat variability. The occurrence and the significance of reinnervation remain controversial. METHODS AND RESULTS: We monitored the evolution of heart rate variability (HRV) after heart transplantation, starting from a few weeks postoperatively up to 10 years after surgery. Twenty-four-hour Holter recordings of 216 heart-transplant patients were analyzed using time and frequency domain analysis of HRV. Analysis of all data revealed an increase in 24-hour and night-time total power starting from 2 years after transplantation. Low-frequency oscillations calculated over the total 24 hours, day- and nighttime increased significantly starting from year 4 and onward (year 4-8: P < 0.005). No evolution was found in high-frequency power. Subgroup analysis revealed a group with a clear spectral component (n = 16), a group with a small component (n = 124), and a group with a flat spectrum (n = 76). Only the first group revealed an evolution in both high- and low-frequency power. CONCLUSION: These results indicate three different types of evolution in HRV, with reinnervating patterns present in only a minority of the patients. The vast majority of the patients show no signs of reinnervation.