The pathophysiology of functional dyspepsia (FD) is unknown and several mechanisms associated with specific symptom patterns have been recently proposed. Increased duodenal acid exposure has been supposed to be associated with nausea, but recently an increase of severity of several dyspeptic symptoms was noted in a subset of dyspeptic patients. As its pathogenetic role is still unclear, we evaluated an involvement of duodenal acid exposure in symptom generation by inducing a hyperacidity status of the duodenum. Twelve young adult healthy volunteers in a randomized, double-blind protocol, underwent duodenal acid (0.2 N, 5 mL min(-1)) or saline perfusion, antropyloroduodenal manometry and duodenal pH monitoring both during fasting and postprandially. Every 15 min, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analogue scale. During acid perfusion, symptom scores for discomfort, bloating, nausea, epigastric burning were significantly higher (P < 0.01) compared to saline. Postprandial antral motility index was lower (2.96 +/- 1.8 vs 3.62 +/- 1.8, P = 0.01) and jejunal motility index higher (4.87 +/- 1.0 vs 4.37 +/- 1.4, P = 0.01) during acid perfusion. Occurrence and duration of phases III of the migrating motor complex showed no difference. Duodenal acid perfusion causes a sensitization to dyspeptic symptoms and induces antral hypomotility and jejunal hypercontractility. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms.