To diagnose fundic atrophic (type A) gastritis as part of the clinical investigation of various diseases or for epidemiologic purposes, a simple and reliable diagnostic test would be of great value. We studied circulating levels of pepsinogen A (PGA) and pepsinogen C (PGC) in 179 patients with fundic atrophic gastritis, 29 unselected patients with gastric adenocarcinoma, 15 totally gastrectomized patients, and 50 gastroscopically examined normal controls. Of 147 patients with severe atrophic gastritis, 42 (29%) had serum PGA and 22 (15%) serum PGC values within the range of those in totally gastrectomized patients. The most sensitive test for fundic atrophic gastritis was the PGA/PGC ratio in serum, the sensitivity and specificity being 99% and 94%, respectively (discrimination limit, 5.5). Correspondingly, the positive predictive value was 98%, and the negative predictive value 98%. Of 29 unselected patients with gastric adenocarcinoma 22 (76%) had serum PGA/PGC values lower than the discrimination limit for atrophic gastritis. We conclude that the relatively simple analysis of PGA and PGC in serum is a powerful test for fundic atrophic gastritis with several potential areas of application.