Neurally mediated syncope may occur in patients whose hemodynamic picture does not fit the characteristics of orthostatic intolerance as described elsewhere in this issue. Nonetheless, patients who suffer from neurocardiogenic or vasovagal syncope may be seriously incapacitated by their episodes of syncope or presyncope. Although it has been assumed that vagal activation as a result of stimulation of ventricular mechanoreceptors is essential to the production of these episodes, several critical observations are presented that suggest that other mechanisms may also be operative in some patient subsets. In addition, evidence is presented that the sympathetic responses of many of these patients may be reduced rather than increased and that abnormal baroreflex responsiveness may also play an causative role. These findings suggest new avenues for therapy in this field in which carefully controlled, randomized, double-blind trials are scarce.