Occasionally, the cardioinhibitory response may be profound during tilt induced syncope. Whether this response is associated with more severe symptoms or predicts a poor response to pharmacotherapy remains controversial. The aim of this study was to characterize patients with vasovagally mediated asystole occurring during head-up tilt test and to evaluate the respective interests of sequential pacing and beta-blockers to treat them. We performed 60 degree tilt testing in 179 consecutive patients with unexplained syncope (91 women and 88 men, age 36.6 +/- 20.1 years). Asystole was defined as a ventricular pause > 5 seconds. All patients with tilt induced asystole received therapy with either beta-blockers or sequential pacing, the efficacy of which was evaluated with serial tilt tests. Of 77 patients with positive tilt test, 10 developed syncope related to asystole (mean duration 11.9 +/- 4.9 s), 2 with spontaneous recovery, and 8 with seizures needing a brief cardiopulmonary resuscitation. When compared with patients without asystole, asystolic patients had more severe symptoms (seizures: 6/10 vs 9/67, P = 0.05, injury 9/10 vs 27/67, P = 0.0048). In the first six patients in whom cardiac pacing was considered, syncope or presyncope still occurred despite atrioventricular pacing at 45 beats/min. Five of these 6 patients, as well as the remaining 4 asystolic patients, were tilted with beta-blockers: 3 patients became tilt-negative; 3 were significantly improved; and 3 did not respond. During follow-up (mean 22.7 +/- 11.7 months) with every patient taking beta-blockers and seven having a permanent pacemaker, no syncopal recurrence was observed. Tilt-induced asystole that may require resuscitative maneuvers occurs especially in patients with a history of seizures or injury. Therapy with beta-blockers in often effective to prevent induction of syncope as well as recurrences.