Guinea pigs were given a daily oral dose of 400 μg/kg of omeprazole or the omeprazole vehicle for 6 weeks. At weekly intervals, the animal and stomach weights were recorded, the nonfasted serum gastrins measured, and the total number of gastric fundic epithelial cells were isolated and counted. Gastric mucous epithelial cells were enriched from the total gastric fundic cell population and cultured for 6 days in the absence or presence of hormones (epidermal growth factor and pentagastrin). We found that omeprazole treatment for 1–6 weeks significantly (p < 0.05) increased the stomach weight, the nonfasted serum gastrin levels, and the total number of isolated gastric fundic and mucous epithelial cells over control animals. A significant (p < 0.05) increase was also found in the basal and hormone-stimulated cultured growth rates of gastric mucous epithelial cells isolated from the stomachs of omeprazole-treated animals as compared with gastric mucous cells from control animals. We conclude that oral omeprazole treatment of guinea pigs will cause a specific increase in the gastric mucous cell population as well as increase the in vitro cultured gastric mucous cell basal and hormone-stimulated growth rat