Long-term treatment with omeprazole induces hyperplasia of enterochromaffin-like cells, closely related to hypergastrinemia. We studied whether proglumide, an antagonist of gastrin/CCK receptor, and enprostil, a synthetic prostaglandin E2 derivative, might inhibit this hyperplasia. Six groups of 8 rats were treated for 10 weeks: a) untreated controls; b) omeprazole 10 mumol/kg; c) proglumide 500 mg/kg; d) enprostil 30 micrograms/kg; e) association of omeprazole and proglumide; f) association of omeprazole and enprostil. Serum gastrin levels were measured at different times during treatment. After sacrifice, fundic argyrophil cells were assessed by Grimelius' staining. Serum gastrin levels and argyrophil cell density were not modified in proglumide- and enprostil-treated groups, as compared with controls. Omeprazole increased significantly these two parameters. When given with omeprazole, proglumide decreased significantly serum gastrin levels and argyrophil cell density, as compared to omeprazole alone, while enprostil did not modify significantly these two parameters. These results indicate that proglumide, but not enprostil, can counteract the omeprazole-induced argyrophil cell hyperplasia in rats.