Recurrent neurocardiogenically mediated episodes of hypotension and bradycardia are a common cause of recurrent syncope that can be identified by head upright tilt table testing. While the use of beta-blockers, theophylline, fludrocortisone, disopyramide, and serotonin re-uptake inhibitors can be helpful in preventing further episodes, some patients are unresponsive to or poorly tolerant of these agents. We investigated the use of the central nervous system stimulant and peripheral vasoconstrictor methylphenidate in preventing both tilt induced and spontaneous neurocardiogenic syncope. Seven patients (all women, mean age 31 +/- 15 years) with recurrent syncope and positive head upright tilt induced hypotension/bradycardia (refractory to normal therapy) were placed on methylphenidate 10 mg orally three times per day. Six of the seven patients became both tilt negative and clinically asymptomatic over a 7-month follow-up period. We conclude that methylphenidate may be an effective therapy in patients with recurrent neurocardiogenic syncope refractory to other forms of therapy.