To characterize the idiopathic postural orthostatic tachycardia syndrome (POTS), we reviewed the records of all patients aged 20 to 51 who presented to the Mayo Autonomic Reflex Laboratory and who exhibited tachycardia at rest or during head-up tilt. These patients were usually women who experienced an acute onset of persistent lightheadedness and fatigue or gastrointestinal dysmotility. In seven patients, a viral illness may have preceded the onset of symptoms. In two instances, signs and symptoms of a small-fiber sensory neuropathy were present. Laboratory evaluation of autonomic function revealed increased diastolic blood pressure to tilt (5/16), increased Valsalva ratio, marked decrease in phase II of the Valsalva maneuver with normal phase IV overshoot, and normal forced respiratory sinus arrhythmia. Abnormal quantitative sudomotor axon reflex test and thermoregulatory sweat test and an excessive orthostatic increase of catecholamines were found in some patients. We conclude that in many instances POTS may be a manifestation of a mild form of acute autonomic neuropathy.