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Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. Autonomic dysfunction has been a postulated mechanism for the pathogenesis of this disorder in children but has not been explored in adults. Our goals were to investigate autonomic nerve function in adult patients with CVS. The sympathetic nervous system was evaluated through postural changes in heart rate and blood pressure and sympathetic skin response in the hand and foot. The parasympathetic nervous system was tested through heart rate response to deep breathing [expiration/inspiration (E/I)], Valsalva and postural indices (30 : 15 ratio). All patients had a 4-h standard isotope labeled egg beater meal gastric emptying test (GET). Twenty-two adult (18 female), mean age 35 ± 11 (range 19-61 years), who met Rome III criteria for CVS were included. History of migraine headache was reported in three patients. Five (23%) had pediatric onset. Of 21 patients who completed the test, nine patients had 21 abnormalities detected in their autonomic nerve testing profile and the remaining 12 had normal autonomic function results. Orthostatic tachycardia was observed in two (mean heart rate increase 39 beats min) and a decline in blood pressure (BP) in three patients (mean BP drop 30/14 mmHg). Parasympathetic abnormalities were elicited in six patients with an abnormal response to deep breathing and E/I index <1.25. Sympathetic nerve dysfunction was reported in seven patients with absent sympathetic skin response in the foot and/or hand. Twelve (57%) of CVS group had rapid GET (<50% retention at 1 h). The frequency of abnormal autonomic nerve function was not significantly higher in rapid GET subgroup. (i) Autonomic nerve dysfunction is common in adult CVS patients, being observed in 43% of our cohort; (ii) Sympathetic abnormalities dominate; and (iii) Rapid gastric emptying, present in 57% of patients, did not correlate with autonomic testing results. These new data provide more insight into the pathophysiology of CVS in adults and help explain the spectrum of clinical manifestations observed in this entity. [ABSTRACT FROM AUTHOR]