Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of nausea and vomiting with complete resolution of symptoms between attacks. Nitric oxide plays a critical role in regulating several components of gastrointestinal mucosal defense and injury. Interleukin-6 has a wide variety of actions in the gastrointestinal apparatus. The purpose of this study was to evaluate the synthesis and release of nitric oxide and interleukin-6 by the esophageal and gastric mucosa in 10 children with cyclic vomiting syndrome, during symptom-free periods, and in 10 controls. The nitric oxide and interleukin-6 release by esophageal mucosa cells obtained from cyclic vomiting patients was quite similar to that in controls, but the release of nitric oxide from gastric mucosa cells of patients was significantly higher than that of controls. Conversely, no interleukin-6 was detectable in gastric mucosa cell supernatants in any of the patients. Further studies are needed to evaluate the relationship between factors triggering cyclic vomiting syndrome and the release of nitric oxide and interleukin-6 by gastric mucosa.