Objective: We studied 146 patients with peptic ulcer disease (n = 72), antral gastritis (n = 58), or duodenitis (n = 16) to ascertain whether the cytotoxic genotype of Helicobacter pylori (Hp) is associated with peptic ulcer disease and/or antral gastritis and whether it influences the circulating levels of total anti-Hp antibodies, anti-cagA antibodies, and pepsinogens. Methods: A gastric juice sample was obtained from each patient, After DNA extraction, polymerase chain reaction was used to amplify the genes urease A (ureA), cagA, and vacA of Hp, Results: A significant association was found between peptic ulcer disease and the cytotoxic genotypes, characterized by the presence of s1 and m1 alleles of vacA and by cagA, Patients with a cagA-positive genotype showed a significant increase in anti-cagA antibodies and also had significantly increased circulating levels of pepsinogen C. Conclusions: Cytotoxic Hp strains are mainly involved in determining peptic ulcer disease, but not antral gastritis, The higher levels of circulating pepsinogen C found in patients infected with cytotoxic genotypes may reflect the higher degree of inflammation sustained by these strains. (C) 1998 by Am. Coll. of Gastroenterology.