To study the efficacy of medical treatment for preventing syncopal recurrences in patients affected by tilt-induced neurally mediated syncope, a randomized placebo-treatment prospective study was performed in 30 patients (10 men and 20 women, mean age 42 +/- 21 years) who had syncope reproduced in 2 consecutive head-up tilt-table tests without pharmacologic intervention (n = 20) or during isoproterenol infusion (n = 10). Patients were randomly assigned to 2 groups: 15 to placebo, and 15 to drug therapy (determined on the basis of serial pharmacologic tilting tests). Therapy was either atenolol (n = 7), dihydroergotamine (n = 2), domperidone (n = 2), cafedrine (n = 1), or elastic compression stockings, alone or in association with drugs (n = 3). During a mean of 10 +/- 7 months of follow-up, syncope recurred in 3 patients (20%) in the treatment group and in 4 (27%) in the placebo group; actuarial rates of absence of syncopal recurrences after 20 months were 70 and 67%, respectively. Thus, the outcome of either treated or untreated patients was favorable (with a low recurrence rate of syncope), and the usefulness of tilting-guided medical therapy remains uncertain.