In this prospective study, the autonomic modulation of the sinus node of 12 patients (mean age 28 +/- 7 years) suffering from vasovagal syncope (VVS) was compared to that of 11 sex and age matched control patients (mean age 32 +/- 4 years) by analysis of heart rate variability. Spectral indices (low frequency power [Plf], high frequency power [Phf], total power [Pt], sympathovagal balance [LF/HF]) and temporal indices, the mean of all coupling intervals between normal beats (mRR), the standard deviation about the mean (sdRR), the percentage of adjacent R to R intervals differing by more than 50 msec (pNN50), and the root mean square of variations in successive R to R intervals (rMSSD) were compared at baseline and during head-up tilt between and within groups. Baseline results were similar in both groups. During tilt testing, comparison of results between groups revealed only significantly higher sdRR and rMSSD and lower LF/HF ratio in VVS patients. Within VVS patients, comparison of temporal and spectral analysis between baseline and tilt showed a significant increase of most indices (Plf, Phf, Pt, sdRR, and rMSSD) but a comparable LF/HF ratio; in contrast, control patients exhibited only a significant increase of LF/HF ratio. In conclusion, VVS patients who developed vasovagal syncope during head-up tilt demonstrated a nonreciprocal modulation of the sinus node by the autonomic nervous system indicative of a pronounced physiological sympathetic surge along with a paradoxical vagal input to the cardiovascular system.