OBJECTIVE: The aim of this study was to determine whether or not heart rate variability (HRV) analysis during the first 20 min of head-up tilt testing could predict whether patients will develop syncope after nitroglycerine administration. DESIGN: 64 patients with previous loss of consciousness underwent head-up tilt testing with the Italian protocol, which involves the administration of nitroglycerine after 20 min of tilt. HRV parameters were analysed from 5 min intervals selected during pretest supine rest (phase 1), the first 5 min (phase 2) and the last 5 min (phase 3) of passive 20 min of tilting, prior to the administration of nitroglycerine. Differences in power (ms(2)) of the spectral components between the various phases of tilting were calculated for each patient and expressed as Delta. RESULTS: 20 patients (group 1, 9 women, mean age 43.2+/-24.5 years) had a syncope during tilt testing after nitroglycerine, while the other 44 (group 2, 24 women, mean age 41+/-20.5 years) did not. In group 1, the HRV spectral parameters high frequency (HF) and total power (TP) had a significant decrement from phases 2 to 3 (p=0.012 and 0.027, respectively), while in group 2 the average HF and TP values did not change. The Delta of spectral parameters between phases 2 and 3 were able to differentiate between the two groups and to predict syncope after nitroglycerine administration (p<0.05). CONCLUSIONS: HRV analysis within the first 20 min of passive tilting demonstrated that patients with nitroglycerine-induced syncope are characterised by a progressive decrement of parasympathetic activity, which does not occur in patients with a negative response to nitroglycerine. If confirmed on a wider population, HRV analysis could replace nitroglycerine administration and shorten the duration of the tilt test.