Tricyclic antidepressants (TCAs) have been usedsuccessfully in the treatment of irritable bowelsyndrome and unexplained chest pain. Little informationis available regarding their use in other functional gastrointestinal disorders. Clinical chartswere analyzed from 37 outpatients (mean age 45 ±2 years, 25 females/12 males) with chronic nausea andvomiting that could not be explained by any conventional organic disorder (mean duration of symptoms 28± 8 months). Twenty-one (57%) had chronicpersistent symptoms; 16 (43%) had intermittent relapsingsymptoms; 13 (35%) also had pain as a dominantcomplaint. Each patient had been treated with TCAsspecifically for the gastrointestinal symptoms(amitriptyline, desipramine, nortriptyline, doxepin, orimipramine), and the subject group was followed for 5.4± 1.1 months. Response (at least moderate symptomreduction using a priori chart rating criteria) occurredin 31 patients (84%), and complete symptom remissionoccurred in 19 (51%)-in 41% with the first TCA trial. Dose at response averaged 50 mg/day,and outcome was unrelated to TCA used. Logisticregression analysis revealed that pain dominanceinterfered with remission (P = 0.03), but other clinical characteristics were not predictive of outcome.This uncontrolled clinical experience indicates that theopen-label response rate of functional nausea andvomiting to low dosages of TCAs resembles that noted in irritable bowel syndrome. TCAs shouldbe studied in controlled fashion for this and relateddyspeptic syndromes, as the success of other treatmentsis limited.