The reappearance of cardiac innervation after cardiac transplantation remains a matter of debate. We evaluated the ability of heart rate variability (HRV) analysis to detect the extent and time course of functional cardiac allograft reinnervation. Time- and frequency-domain analysis of heart rate was performed on Holter recordings of 120 heart transplant and four heart-lung transplant recipients. A high frequency (HF) component was clearly distinguished on visual inspection of power spectral density in 42 patients. In eight patients an HF component of normal magnitude was detected. The other 34 patients in this group, including all four heart-lung transplants, presented with a very small HF component. The other 82 patients showed a flat spectrum. The group with an HF component of normal amplitude was significantly different, compared to the other groups, for all HRV parameters. Serial plotting of HRV parameters of the patients with an HF component of normal amplitude against time posttransplant, revealed, from 12 months onwards, a progressive increase of parameters denoting HF variability. In five heart transplant patients with acute allograft rejection, the use of HRV analysis for rejection monitoring was unsuccessful. These results suggest that, inasmuch as the HF component of HRV is caused by parasympathetic cardiac innervation, the HF component of normal amplitude, observed in only a minority of cardiac transplant recipients (6%), is a marker for parasympathetic reinnervation. The evolution over time of this HF component is compatible with a biological phenomenon as gradual parasympathetic reinnervation of the sinus node.