Recent studies indicate that expression of mitogen-inducible cyclooxygenase-2 (COX-2) occurs in gastrointestinal tumors. We investigated the effects of Helicobacter pylori (H. pylori) infection, a class I carcinogen for the human stomach, on gastric COX-2 expression using immunohistochemistry. Human subjects without macroscopic lesions, as determined by endoscopic screening, were biopsied for H. pylori infection. The biopsy samples were immunohistochemically examined for COX-2 expression. COX-2 was expressed in gastric epithelia and subepithelial inflammatory cells in all H. pylori-infected subjects. There was no expression of COX-2 in the gastric mucosa of H. pylori-negative subjects. COX-2 expression has been reported in gastrointestinal carcinomas, gastrointestinal cancer cell-lines, and in the gut after carcinogenic treatment. The present study demonstrates that H. pylori infection leads to gastric mucosal expression of COX-2, indicating that the enzyme is involved in H. pylori-related gastric pathology in humans.