BACKGROUND: Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released from the stomach. Animal studies suggest that ghrelin stimulates gastrointestinal motor activity. AIM: To investigate the influence of ghrelin on gastric emptying rate and meal-related symptoms in idiopathic gastroparesis. METHODS: In six patients with idiopathic gastroparesis, a breath test was used to measure gastric emptying rates (t(1/2)) for solids and liquids after administration of saline or ghrelin 40 microg/30 min in a double-blind, randomized fashion. At each breath sampling, the patient was asked to grade the intensity of six different symptoms (epigastric pain, bloating, postprandial fullness, nausea, belching and epigastric burning) and these were added to obtain meal-related symptom severity score. RESULTS: Ghrelin significantly enhanced liquid emptying (t(1/2): 86 +/- 7 vs. 53 +/- 6 min, P = 0.02) and tended to enhance solid emptying (144 +/- 45 vs. 98 +/- 15 min, P = 0.06). Ghrelin pre-treatment significantly decreased cumulative meal-related symptom score (196 +/- 30 vs. 136 +/- 23, P = 0.04) and individual scores for fullness (55 +/- 8 vs. 39 +/- 8, P = 0.02), and for pain (40 +/- 8 vs. 16 +/- 5, P < 0.05). CONCLUSIONS: In idiopathic gastroparesis, administration of ghrelin enhances gastric emptying and improves meal-related symptoms. These observations suggest a potential for ghrelin receptor agonists in the treatment of gastroparesis.