Tricyclic antidepressants (TCAs) have been used successfully in the treatment of irritable bowel syndrome and unexplained chest pain. Little information is available regarding their use in other functional gastrointestinal disorders. Clinical charts were analyzed from 37 outpatients (mean age 45 +/- 2 years, 25 females/12 males) with chronic nausea and vomiting that could not be explained by any conventional organic disorder (mean duration of symptoms 28 +/- 8 months). Twenty-one (57%) had chronic persistent symptoms; 16 (43%) had intermittent relapsing symptoms; 13 (35%) also had pain as a dominant complaint. Each patient had been treated with TCAs specifically for the gastrointestinal symptoms (amitriptyline, desipramine, nortriptyline, doxepin, or imipramine), and the subject group was followed for 5.4 +/- 1.1 months. Response (at least moderate symptom reduction using a priori chart rating criteria) occurred in 31 patients (84%), and complete symptom remission occurred in 19 (51%)--in 41% with the first TCA trial. Dose at response averaged 50 mg/day, and outcome was unrelated to TCA used. Logistic regression analysis revealed that pain dominance interfered with remission (P = 0.03), but other clinical characteristics were not predictive of outcome. This uncontrolled clinical experience indicates that the open-label response rate of functional nausea and vomiting to low dosages of TCAs resembles that noted in irritable bowel syndrome. TCAs should be studied in controlled fashion for this and related dyspeptic syndromes, as the success of other treatments is limited.