Because of the cardiac denervation, transplanted heart represents a reference model for the study of the autonomic control of the heart. Heart rate (HR) variability analysis has been proposed as a method for assessing the vagus — sympathetic influence on the heart. In this study, both circadian and beat-tobeat HR variability was investigated in 24-hour Holter monitoring from 8 orthotopic cardiac transplant recipients, and 8 normal subjects. Circadian rhythm of HR was assessed by computerised periodic analysis, while beat-to-beat HR variability was assessed by autoregressive power spectrum analysis. Average 24-hour HR of transplanted heart was higher but not statistically different from controls. A significant circadian rhythm of HR was found in all controls and in all but one transplanted patients (pts). The semiamplitude of the periodic function was significantly lower in transplanted pts than in controls. A beat-to-beat variability was also present in all transplanted pts; as compared to normal subjects 1) the total R-R spectral power was markedly reduce (p < .01) throughout the 24-hour period, 2) the HR variability at the ‘very low’ frequencies (VLF: ≤ .05 Hz) was markedly reduced (p < .01) while it was preserved in the ‘low’ (LF: up to .14 Hz), and in the ‘high’ respiratory frequency range (HF: .15 to .35 Hz) in all pts, particularly during the night (the power spectrum of R-wave amplitude, an indirect marker of respiration, allowed the identification of peaks related to respiration in the spectra of transplanted heart). In conclusion, in cardiac transplantation, a persistence of HR variability can be shown in spite of heart denervation. While the persistence of circadian rhythm of HR may be attributed to a parallel oscillation in blood cathecolamine levels and its attenuation to the absence of nervous reinforcement, beat-to-beat fluctuations (namely at HF, and possibly at LF) might be interpreted as the result of intrinsic cardio-cardiac reflexes, elicited by changes in atrio- ventricular volume and/or pressure load.