OBJECTIVE: Cyclic vomiting syndrome (CVS) has been described infrequently in adults, and treatment in both children and adults remains unsatisfactory. We report clinical features of a group of adults with CVS and anecdotal outcome from open-label treatment with tricyclic antidepressants, medications that have some efficacy in other unexplained gastrointestinal disorders. METHODS: Clinical data were examined from 17 adult patients with CVS seen over a 10-yr period, each having been treated with a tricyclic antidepressant. Outpatient records were reviewed, clinical outcome was extracted using a priori criteria, and findings were compared with 37 patients having usual functional nausea and vomiting who also received tricyclic antidepressant therapy. RESULTS: Symptoms in CVS began at age 35 yr (range 14-73 yr); the average episode length was 6 days (range 1-21 days) and the symptom-free interval averaged 3.1 months (range 0.5-6 months). Vomiting cycles typically began without warning, and fewer than one-third of the subjects reported a prodrome or potential trigger event, such as menstrual periods, pregnancy, or large meals. Sleep was seemingly beneficial in 23.5%. Tricyclic antidepressant therapy was associated with complete remission in 17.6% and partial response in 58.8%, but was less effective than for functional nausea and vomiting (p = 0.02). CONCLUSIONS: CVS is a rare diagnosis with distinctive features in adults. Duration of episodes and cycles varies considerably across subjects. In open-label, uncontrolled use, tricyclic antidepressants appear beneficial for some subjects but are less effective in CVS than in chronic, persistent functional nausea and vomiting.