Secretory group IIa phospholipase A(2) (PLA(2)-II) is an important regulator of proinflammatory lipid mediator production and may play a role in ileal inflammation in Crohn's disease. The enzyme has previously only been detected in epithelial Paneth cells. However, one characteristic feature of Crohn's disease is the transmural inflammation. Full thickness ileal sections from nine patients with Crohn's disease, and histologically normal sections from patients with colonic cancer (n=7) and chronic severe constipation (n=1) as controls, were used in this study. PLA(2)-II-positive cells were detected by immunofluorescence and in situ hybridization. Metachromatic staining and esterase staining were used to identify mast cells and macrophages, respectively. It was shown that mast cells and macrophages in the ileal submucosa in both patients and controls showed positive PLA(2)-II staining. The number of PLA(2)-II-labeled cells that did not react with metachromasia, e.g. macrophages, was significantly greater in inflamed Crohn's disease compared to controls. This is, to our knowledge, the first study that has described the presence in healthy, while presence and upregulation of PLA(2)-II-positive cells in inflamed human ileal submucosa. Our findings suggest a proinflammatory potential for secretory PLA(2)-II in submucosa, while proinflammatory stimulation of mast cells and macrophages in vitro has shown that the enzyme is responsible for delayed prostaglandin formation.