Fasting and meal-stimulated serum gastrin and serum pepsinogen I levels were determined in 8 healthy volunteers before, during, and after administration of 30 mg of omeprazole daily for 14 days. Fasting levels and the integrated increment of serum gastrin were significantly increased after 7 and 14 days of treatment with omeprazole, but not after a single dose. Fasting levels measured 2, 4, 7, 14, and 21 days after stopping treatment with omeprazole and the integrated increment of serum gastrin determined 7 and 14 days after discontinuation of omeprazole were not significantly different from pretreatment levels. Fasting serum pepsinogen I levels increased progressively during omeprazole treatment. This increase was significant after 7 and 14 days of treatment and 2 and 4 days after discontinuing omeprazole. These levels were not significantly different from pretreatment levels 7, 14, and 21 days after omeprazole treatment. Serum pepsinogen I did not significantly change after the test meal. It is concluded that fasting and meal-stimulated serum gastrin levels and fasting serum pepsinogen I levels increase significantly during treatment with 30 mg of omeprazole daily for 14 days, but after stopping treatment there is a rapid return to pretreatment levels.