This study was undertaken to clarify the relationship between marked elevation of plasma carcinoembryonic antigen (CM) and signet ring cell carcinoma of the stomach. METHODS. To elucidate the contributing factor of extreme elevation of plasma CEA value, the histologic and biochemical records for 3 10 cases of stomach carcinoma, including 202 advanced and 108 early, collected between 1980 to 1994 from the San-in Rosai Hospital and Tottori University Hospital were studied. Immunohistochemical localization of CEA in the stomach was performed using a peroxidase antiperoxidase (PAP) staining technique. RESULTS. Among 310 cases of gastric carcinoma, 44 (14%) had abnornial plasma CEA values. The positivity rates of early and advanced gastric carcinoma were 3.7% (41 18) and 19% (40/202), respectively. Concerning advanced gastric carcinoma, 20 cases had more than 51 ng/mL, and 20 cases had between 5 ng/mL and 50 ng/ mL. Four cases with plasma CEA values of more than 1,000 nglmI. had histological signet ring cell carcinoma (one case), and poorly differentiated adenocarcinoma with signet ring cell carcinoma (2 cases). Three cases of signet ring cell carcinoma or poorly differentiated adenocarcinoma of the stomach were massive local infiltration rather than hepatic metastasis. Among 40 cases with elevated plasma CEA. a multivariate regression analysis showed that only one variable (lymph node metastasis) was an independent factor ( P < 0.05). Significantly higher rates of peritoneal metastasis ( P < 0.0001) and lymph node metastasis ( P i 0.05) were observed in patients with marked elevations of plasma CEA than in patients with moderate elevations of plasma CEA. No correlation was obtained between plasma CEA value and several biochemical tests. CONCLUSIONS. Marked elevation of plasma C f 3 may be found in the absence of liver metastasis from signet ring or poorly differentiated gastric carcinoma. Patients with marked elevations of CEA also had lymphatic and peritoneal dissemination.