Dopamine antagonists are effective anti-emetics. Domperidone does not readily cross the blood-brain barrier and is less likely to cause central nervous system side-effects than metoclopramide. However, a direct comparison of the safety and efficacy of the two drugs has not hitherto been made. Ninety-five patients, with symptoms of nausea and vomiting due to a variety of oesophageal or gastric disorders, were recruited into a randomised, double-blind, three-part, parallel-group comparative study of controlled release metoclopramide 15 mg (Gastrobid Continus tablets, Napp Laboratories) given twice daily, and domperidone 10 mg or 20 mg given three times daily. Assessments for nausea, vomiting, reflux symptoms and adverse events were made on entry to the study. Patients were randomly allocated to one of the three treatment regimes for a period of seven days, throughout which daily symptomatology and use of escape medication were recorded on a diary card. At the end of the treatment period, nausea, vomiting and reflux symptoms, adverse events and a global assessment of patients' symptom control were recorded by the investigator. Both controlled release metoclopramide and high and low dose domperidone significantly reduced symptoms of belching, flatulence, distension, heartburn, regurgitation, reflux, nausea and vomiting compared to baseline. There were no significant differences between the three treatments in efficacy or in the number and severity of side-effects.