Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2–4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.