In the present study, gastric pH was lowered by hydrochloric acid to investigate whether the cause of enterochromaffin-like(ECL) cell hyperplasia was due to the inhibition of acid secretion by omeprazole or due to the direct action of the drug. Omeprazole was given to female Crj:CD(SD) rats in a daily oral dose of 2 or 8 mg/kg for 13 weeks, and 20 ml/kg of 0.12 N HCl was further given orally to the animals 3 and 6 hours after each dosing. The animals were killed at the end of the dosing period, and the stomach was removed and weighed. The thickness of the gastric wall was measured and ECL cell count and area rate of the cells were calculated with an image analyzer. There were no effects of the treatment with HCl on stomach weight or thickness of the gastric wall, but ECL cell count and area rate of the cells decreased markedly by the treatment with HCl. Therefore, the cause of gastric ECL cell hyperplasia induced by omeprazole was suggested to be sustained high gastric pH levels.