Functional dyspepsia (FD) symptoms may develop after an acute gastroenteritis. In post-infectious (PI) irritable bowel syndrome, persisting low-grade colonic inflammation and increased enterochromaffine cells (EC) counts have been reported. The aim was to compare signs of inflammation and EC hyperplasia on duodenal biopsies in presumed PI-FD and unspecified-onset (U-)FD. Duodenal biopsies were obtained in 12 U-FD and 12 PI-FD (on average 13 months after the acute event) patients. The presence of intra-epithelial, intravillar, and the number of CD3, CD4, CD8 and CD68+ cells per crypts, and the mean number of Chromogranine A (CA) positive cells per villus were compared. We also measured gastric emptying and assessed proximal stomach function with a barostat. Data are shown as mean +/- SEM. Focal aggregates of T cells and focal CD8+ aggregates, were found in PI-FD but not in U-FD patients (respectively 5/12 vs 0/12, P = 0.02 and 5/9 vs 0/11, P < 0.01). In patients with focal aggregates, gastric emptying was delayed (189 +/- 37 min vs 98 +/- 11 min, P = 0.002). The number of CD4+ cells per crypt (0.52 +/- 1.6 vs 1.22 +/- 2.18, P = 0.04), and the number of intravillar CD4+ cells (0.5 +/- 0.2 vs 2.7 +/- 0.7, P = 0.01) were reduced, while the number of CD68+ cells per crypt was increased (0.64 +/- 0.13 vs 0.40 +/- 0.05, P = 0.03) in PI-FD. The number of EC and CA were comparable. PI-FD is associated with persisting focal T-cell aggregates, decreased CD4+ cells and increased macrophage counts surrounding the crypts. This may indicate impaired ability of the immune system to terminate the inflammatory response after acute insult.