BACKGROUND/AIMS: Long-term use of proton pump inhibitor (PPI) induces hypergastrinemia, which results from the suppression of gastric acid secretion. Hypergastrinemia causes enterochromaffin-like (ECL) cell hyperplasia, which is a predisposing factor of carcinoid tumor of stomach. The aim of this study was to identify the effect of long-term gastric acid suppression on the gastric peptides levels, such as gastrin, chromogranin A, or ghrelin. METHODS: Control group included patients who had no medication over six months. Both H2RA (H2 receptor antagonist) and PPI groups had medication at least for six months. Fasting blood was taken from each patient to assay serum gastrin, chromogranin A, and ghrelin by RIA and ELISA techniques. RESULTS: The patients with the above reference range of serum gastrin and chromogranin A were more commonly found in PPI group compared to control and H2RA group. However, serum ghrelin level was within the reference range in all the patients regardless of groups. There was no difference in the ratio of serum gastrin/chromogranin A among three groups. Both average serum levels of gastrin and chromogranin A were significantly elevated in PPI group compared to control and H2RA group. There was a significant correlation between the level of serum gastrin and chromogranin A. CONCLUSIONS: Long-term administration of H2RA does not affect the serum gastrin and chromogranin A level. However, long-term administration of PPI increases serum gastrin and chromogranin A. Ghrelin may influence gastric acid secretion in other pathway than ECL cell-mediated pathway such as gastrin or chromogranin A.