Background and Objectives: Epidemiological studies have suggested that the regular use of nonsteroidal antiinflammatory drugs, which inhibit cyclooxygenase (COX), reduces the risk of colon cancer. The inducible COX-2 isoform has been reported to be upregulated in colorectal carcinomas and may play a role in colorectal carcinogenesis. The purpose of this study was to investigate the expression of COX-2 protein in human gastric adenocarcinomas. Methods: COX-2 protein expression was examined in 23 patients with gastric adenocarcinoma by immunoblotting and immunohistochemistry. Results: There was an increase in COX-2 protein levels in 19 of the 23 carcinomas (83%) compared with the paired normal gastric mucosa by an immunoblot analysis. There was no correlation between tumor histology and COX-2 protein expression. An immunohistochemical study in the 19 cases showed diffuse COX-2 staining in the cytoplasm of cancer cells. Mononuclear cells or fibroblasts of the cancer stroma were not stained with COX-2. Sporadic staining for COX-2 was observed in the normal fundic or metaplastic glandular cells in all cases. Conclusions: COX-2 protein expression was elevated in most human gastric adenocarcinomas in comparison to the normal mucosa. COX-2 may therefore play an important role in gastric carcinogenesis.