Serum pepsinogen I and pepsinogen II levels in 369 healthy controls, 38 duodenal ulcer, 30 gastric ulcer and 46 stomach cancer including 21 early and 25 advanced gastric cancer patients were measured by enzyme-linked immunosorbent assays using pepsin moiety-reacting monoclonal antibodies to pepsinogens I and II. Serum pepsinogen I and pepsinogen II levels were higher in the duodenal and gastric ulcer groups than in the control. Although there was no significant difference in serum pepsinogen II between stomach cancer and control, serum pepsinogen I was significantly lower in the former than in the latter and also in advanced gastric cancer than in early gastric cancer. A specific negative correlation of serum pepsinogen I with patient age was observed in stomach cancer but not in peptic ulcer or control groups. Receiver operating characteristic analysis was performed and indicated that serum pepsinogen I, compared with serum pepsinogen II or the pepsinogen I/pepsinogen II ratio, is the most effective marker for stomach cancer.