Impairment of gut barrier function has been demonstrated in patients with severe acute pancreatitis and may contribute to the development of local and systemic septic complications. The underlying mechanisms, however, remain unclear. Against this background, our aims were to investigate the small intestinal epithelial morphology and mucosal immunity in patients with severe acute pancreatitis.|Segments of terminal ileum from three patients with severe necrotizing acute pancreatitis who underwent pancreatic debridement and ileocolic resection for doubtful or evident segmental colonic viability were available for the study. Control specimens were available from seven patients who underwent gastric bypass and distal ileal resection for morbid obesity. Sections were cut and stained with hematoxylin and eosin for the measurement of villous height and crypt depth, and with toluidine blue for the determination of mucosal mast cell counts. Only adequately oriented specimens were deemed suitable for computer-aided image analysis. Results were expressed as the villous height/crypt depth ratio (VH/CD) and mucosal mast cell index (ratio of mast cell count/length of muscularis mucosa).|Microscopy of the small intestine from controls was normal. The villous height and VH/CD were significantly reduced in patients with acute pancreatitis compared with controls (median, 0.47 mm vs 0.68 mm, and 1.9 vs 2.8, respectively; P < 0.00001). The mast cell index was significantly reduced in patients with acute pancreatitis compared with controls (median, 5.88 cells/mm vs 8.58 cells/mm; P= 0.001). A positive correlation was observed between the mast cell index and the height of the villi ( r= 0.23; P= 0.027).|Patients with necrotizing acute pancreatitis have an altered intestinal morphology and depleted mucosal mast cells. These factors may contribute to the impairment of gut barrier function in patients with severe acute pancreatitis.