Among 7498 Japanese men who were examined from 1967 to 1970, 48 were subsequently diagnosed with stomach cancer and had premorbid stored sera available for serum pepsinogen I analysis. The median interval between serum collection and diagnosis of cancer was 44.5 months (range, 3 to 103 months). A low pepsinogen I level was found in 15 of the 48 patients with stomach cancer and in only six (6.3%) of 96 matched control subjects (p < 0.001). All 15 patients with low pepsinogen I levels belonged to the subgroup of 38 who had the intestinal-mixed-other histologic types of gastric cancer. This finding indicates that a low serum pepsinogen I level is a subclinical marker of increased risk for these histologic types of gastric cancer.