BACKGROUND AND AIMS: Although delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia, the efficacy of prokinetic drugs has not been established. Recent studies using macrolide prokinetics were negative but receptor desensitisation may have played a role. The aim of the present study was to evaluate the influence on meal induced symptoms of acutely administered erythromycin in patients with gastroparesis. METHODS: In 20 patients with functional dyspepsia, gastric emptying was studied twice using the (14)C octanoic acid and (13)C glycin breath test to establish the reproducibility of the test. Breath samples were taken before the meal and at 15 minute intervals for a period of 240 minutes postprandially. At each breath sampling, the patient was asked to grade the intensity (0-3) of six dyspeptic symptoms. Twenty four patients (three men, mean age 43.5 (3) years) with dyspeptic symptoms and delayed gastric emptying were studied twice after pretreatment with saline or erythromycin intravenously. RESULTS: Meal related symptom severity scores were reproducible. Treatment with erythromycin significantly enhanced solid and liquid gastric emptying (t(1/2) 146 (27) v 72 (7) minutes, respectively (p<0.01), and 87 (6) v 63 (5) minutes (p<0.001)). Only the severity of bloating was significantly improved by erythromycin (23 (3.9) v 14.5 (2.7); p<0.01); all other symptoms and the cumulative meal related symptom score were not altered by erythromycin. CONCLUSIONS: In a setting where desensitisation played no role, erythromycin enhanced gastric emptying was not associated with a beneficial effect on meal related symptom severity.