Alerting stimuli causing arousal have been shown to elicit a reproducible transient inhibition of muscle sympathetic nerve activity (MSNA) in healthy subjects. The aim of the present study was to test whether this inhibitory response to arousal is exaggerated in patients with a history of vasovagal syncope. We studied 24 untreated syncope patients, 12 of whom met the DSM-IV-TR diagnostic criteria for blood/injury phobia and 18 age-matched healthy subjects. MSNA was recorded from the peroneal nerve at the fibular head. Arousal was induced by randomly presented trains of five electrical pulses delivered to a finger. The pulses were triggered on five consecutive R waves of the ECG, with a delay of 200 ms. Patients also underwent cardiological and neurological examinations, tilt test and a structured interview to investigate diagnostic criteria for specific phobia. The syncope patients had significantly lower resting MSNA (29 +/- 2 bursts/min) and diastolic blood pressure (BP, 78 +/- 2 mmHg) compared to controls (36 +/- 2 bursts/min and 84 +/- 3 mmHg; P < 0.05), whereas no significant differences were found for resting heart rate and systolic BP. The phobic patient group exhibited prolonged sympathetic inhibitions to arousal stimuli compared to controls and non-phobic patients, whereas no difference was found between tilt-positive and tilt-negative patients or between controls and non-phobic patients. The findings suggest that the degree of inhibition in response to arousal stimuli is related to a subjective factor coupled to fear of blood/injury. The exaggerated inhibition in patients with phobia to blood/injury may be a factor predisposing to syncope in those patients.