We have studied 221 adults drawn from an impoverished urban population with high human immunodeficiency virus (HIV) seroprevalence (35%) to determine the prevalence of gastroduodenal pathology and its relationship to serological markers of Helicobacter pylori virulence proteins and other potential environmental and immunological determinants of disease including HIV infection. Eighty-one percent were H. pylori seropositive, and 35% were HIV seropositive. Urban upbringing and low CD4 count were associated with a reduced likelihood of H. pylori seropositivity, as was current Ascaris infection, in keeping with recent evidence from an animal model. One hundred ninety-one adults underwent gastroduodenoscopy, and 14 had gastroduodenal pathology. Mucosal lesions were a major cause of abdominal pain in this population. While the majority of patients with gastroduodenal pathology (12 of 14) were seropositive for H. pylori, none were seropositive for HIV. Smoking was associated with increased risk of macroscopic pathology, and a history of Mycobacterium bovis BCG immunization was associated with reduced risk. Antibodies to H. pylori lipopolysaccharide were associated with pathology. HIV infection was associated with protection against mucosal lesions, suggesting that fully functional CD4 lymphocytes may be required for the genesis of gastroduodenal pathology.