INTRODUCTION AND OBJECTIVES: The underlying mechanism of syncope induced by head-up tilt test is still incompletely understood. It has been proposed a sudden increase in parasympathetic's activity induced by the excessive activation of the cardiac mechanoreceptors. The aim of our study was to evaluate the clinical, electrocardiographic and hemodynamic responses to head-up tilt test before and after treatment with transdermal Scopolamine (anticholinergic agent). METHODS: We studied 17 patients (8 females, 9 males; mean age 43 +/- 19 years) with > or = 2 syncopal episodes of unknown origin and a positive tilt test (a positive response to tilt testing alone or in conjunction with an infusion of isoproterenol was defined as the appearance of syncope or presyncope associated to hypotension and/or bradycardia). Symptoms developed in 12 patients during the baseline tilt (Group I) and in 5 patients after infusion of isoproterenol (Group II). Mean time to symptoms was 8.5 +/- 7.9 minutes in group I. All patients were them treated with transdermal Scopolamine (1.5 mg/24 hours) and 48 hours later tilt test was repeated. RESULTS: In group I, 8 patients (66.6%) became tilt test negative and in the remaining 4 patients mean time before the appearance of symptoms was increased (8.5 +/- 7.9 vs 16.2 +/- 2.5 minutes; p < 0.05). In group II, 3 patients (60%) became tilt test negative and in the remaining 2 patients symptoms developed after an infusion of higher doses of isoproterenol than in the first study. So, with transdermal scopolamine 11 out of 17 patients became tilt test negative and time to symptoms was increased in all of the remaining 6 patients. CONCLUSIONS: Our study suggest that transdermal scopolamine is an usefull treatment in the prevention of neuro-cardiogenic syncope induced by head-up tilt test.