The present study is aimed to investigate the circadian rhythm (CR) of heart rate (HR) in acute rejecting and non-rejecting heart transplanted patients (HTP). The purpose is to provide evidence that an impairment in the HR CR may have a role in predicting episodes of acute rejection in HTP. The study was carried out on 32 Holter monitorings of 13 patients: 9 Holter monitorings were carried out during an episode of acute rejection documented by endomyocardial biopsy. Time data series were analyzed by Cosinor method in order to validate the occurrence of HR CR. The Cosinor analysis found a highly statistically significant HR CR in non-rejecting HTP. The occurrence of the HR CR was not statistically validated in acute rejecting HTP. These findings suggest that the lack of a periodic variability in the 24-hour HR pattern may be useful to diagnose acute heart rejection.