The effect of 60 mg oral omeprazole daily for 9 days on intrinsic factor and gastric acid secretion was studied in eight healthy volunteers. Gastric secretion studies were performed during saline and 0.1 M HCl perfusion before and after omeprazole administration. During dosing with omeprazole, basal gastric acid output diminished by 94%, and pentagastrin-stimulated acid output by 97%. Basal, peak and steady-state stimulated intrinsic factor output were unaffected by omeprazole. It is concluded that high oral doses of omeprazole suppress gastric acid secretion to very low levels but they do not affect intrinsic factor secretion. Intrinsic factor secretion was also unaffected by profound hypochlorhydria.