The effects of omeprazole on developing rat stomach mucosa were investigated. Infant rats were given subcutaneous injections of either omeprazole (25 mg/kg body weight/day) or vehicle once a day from the day after birth. As a result, omeprazole caused an elevation of mucosal pH and suppressed an increase in mucosal pepsinogen and its mRNA levels during stomach development. Histologically, these changes were associated with a reduction in mature pepsinogen-producing cells throughout stomach mucosa. Omeprazole also caused a delay in the expression of cathepsin E in surface mucous cells and an increase in labeled cells with bromodeoxyuridine. Thus, the present results indicate that omeprazole induces an increase in mucosal cell proliferation and delays the differentiation of developing rat stomach mucosa. Since the observed changes were remarkable especially from days 15 to 21 after birth when significant development of acid secretion occurs, the effects of omeprazole appear to be related with the potent acid inhibitory effect of the reagent.