Objectives. The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation.Background. Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high.Methods. Forty patients (age 60 ± 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with 16 control subjects (age 66 ± 13 years, 8 men, 8 women) with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 ° for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 ° by means of short bursts of atrial pacing.Results. Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 ± 32 vs. 127 ± 32 mm Hg), whereas mean heart rate was similar (142 ± 35 vs. 134 ± 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate ≤130 beats/min. At the time of syncope, heart rate decreased (−12 ± 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 ± 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 ± 21 beats/min, p = 0.009).Conclusions. Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.