Background: Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin synthesis, and plays an important role in tumor enlargement. COX-2 is expressed in human gastric and colorectal tumors, and the expression increases in a tumor size-dependent manner. In the present study, we attempted to examine the COX-2 expression pattern in gastric hyperplastic polyp, a non-tumorous lesion. Patients and Methods: Fifty-eight gastric hyperplastic polyps, obtained by endoscopic polypectomy, were immunostained with anti-COX-2 and antivascular endothelial growth factor (VEGF) antibodies. Microvessel density (MVD) was determined by von Willebrand factor immunostaining. Results: In larger gastric hyperplastic polyps, COX-2 was expressed mainly on the luminal side of the polyp stroma, while it was absent in smaller polyps. A significant correlation between COX-2 immunoreactivity and polyp size was observed (p < 0.01). High VEGF expression and MVD were observed mainly in the same stromal region of the polyps where COX-2 was expressed. Both VEGF expression and MVD were also correlated with polyp size significantly (ps < 0.01). Conclusions: COX-2 expression increased in a size-dependent manner in non-tumorous hyperplastic polyps, suggesting that COX-2 expression is not necessarily linked to epithelial cell transformation. Moreover, COX-2 may participate in polyp enlargement through angiogenesis by promoting VEGF production. Copyright (C) 2003 S. Karger AG, Basel.