We investigated serum levels of anti-parietal cell antibody (APCA) in relation to various gastric diseases. Subjects were 224 Japanese patients including 58 with gastric cancer. All patients underwent gastroscopy, and APCA was investigated by enzyme-linked immunosorbent assay. Unexpectedly, there was no difference in APCA levels between patients with gastric cancer and those with gastritis. Among H. pylori-positive patients, APCA levels were closely correlated with grades of atrophy when no gastric cancer was present, but no correlation was found when gastric cancer was present. APCA-negative gastric cancer was found mainly in males and was characterized by massive infiltration of neutrophils in the background mucosa. The 24 patients with gastric cancer were APCA-negative and showed low pepsinogen levels. The odds ratio for the incidence of gastric cancer in these patients was 7.90 (95% CI 3.4-18.4). This suggests APCA-negative gastric cancer is the predominant form of gastric cancer in Japan.