Previous studies in rats have shown that stomach carcinogens cause a decrease of total pepsinogen content and a decrease of the fastest pepsinogen isozymogen in gastric mucosa before the appearance of carcinoma. In man the presence of Pg 5, and in particular a strong Pg 5, appears to be associated with gastric cancer. Low serum PG I levels were found in patients with gastric cancer, atrophic gastritis, intestinal metaplasia and gastric polyp. In this chapter we review the literature and report our results of PG I isozymogen and serum PG I determinations in 500 patients with various gastric disorders. It is concluded that premalignant changes of the stomach are associated with the presence of a strong Pg 5 isozymogen and with a low serum PG I level.