Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are often considered as interchangeable terms. However, the application of power spectral analysis to describe spontaneous fluctuations in heart period has clearly shown that RSA is only a part of HRV, and that in specific situations their respective patterns may diverge. In order to quantify the RSA we have used a mathematical method based on combined spectral analysis of respiration and RR interval (cross-correlation function), and evaluated its performance in terms of reproducibility, sensitivity to parasympathetic withdrawal and in clinical evaluation of autonomic function. Compared to other indices of HRV the cross-correlation between RR interval and respiration showed a greater sensitivity to parasympathetic withdrawal, better reproducibility and a high sensitivity in detecting autonomic dysfunction in diabetic patients. These findings suggest that specific indices of RSA, such as the cross-correlation, can be a valid tool for the diagnostic approach to cardiac autonomic dysfunction.