This study was performed to examine the effectsof additional enprostil administration onhypergastrinemia and gastric acid suppression induced byomeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacterpylori-positive and four Helicobacter pylori-negativepatients) before treatment, after two weeks ofomeprazole (20 mg/day), and after two weeks ofomeprazole and enprostil (50 μg/day). The additionalacid inhibitory effect of enprostil was evaluated by24-hr intragastric pH measurements in five healthyHelicobacter pylori-negative volunteers. Afteromeprazole treatment, the serum gastrin level ofHelicobacter pylori-positive patients (3.5-fold ofcontrol) was markedly higher than that of Helicobacterpylori-negative patients (1.7-fold of control).Additional treatment with enprostil suppressed serumgastrin levels to 0.4-fold and 0.7-fold of omeprazoletreatment levels in Helicobacter pylori-positive andHelicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recordedduring the nonmeal daytime interval increasedsignificantly with additional enprostil. Thus, enprostilreduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positivepatients, and effectively suppresses acidsecretion.