This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 μmol/kg. Omeprazole was given by the same regimen in a dose of 400 μmol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose. Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11 -fold 2 h after dosing and 8- to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole. The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors.