Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. We studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days' omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, whereas it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa.