Cyclooxygenase (COX)-2, an inducible isoform of prostaglandin synthetase, has been reported to be a key molecular target of colon cancer prevention by nonsteroidal anti-inflammatory drugs. Recently, it has been shown that Helicobacter pylori (H. pylori) could induce COX-2 together with inflammatory cytokines. Although human hyperplastic gastric polyps disappeared or decreased in number and size after eradication of H. pylori, the mechanisms in this step, especially the roles of COX-2, have not been yet elucidated. The aims of the present study were to examine the expression and localization of COX-2 in human hyperplastic gastric polyps immunohistochemically. Twelve specimens of human hyperplastic gastric polyps were obtained from endoscopic polypectomy. The expression of the COX-2 protein was immunohistochemically examined on formalin-fixed and paraffin-embedded tissue sections using an anti-COX-2 antibody and an avidin-biotin complex method. Cells expressing COX-2 were further immunohistochemically identified using a specific antibody against macrophages (CD68), and myofibroblasts (alpha-smooth muscle actin). Immunoreactive COX-2 was predominantly and strongly expressed in interstitial cells in the sub-epithelial layer of 10 hyperplastic polyps. Semi-quantitative analysis revealed a significant increase in COX-2 expression in interstitial cells. The staining pattern of macrophages and myofibroblasts partly corresponded to that observed for COX-2 in hyperplastic gastric polyps. These results suggest that COX-2 in mesenchymal cells induced by H. pylori may play an important role in the tumorigenesis of human hyperplastic gastric polyps.