To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylori (H pylori) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylori positive (n = 105) and negative patients (n = 64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylori positive patients (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals 3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001). Similar results were found using lucigenin (which reacts directly with oxygen metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater in H pylori positive compared with negative tissue when samples were grouped by equivalent macroscopic or microscopic damage. This difference was in part accounted for by a greater neutrophil infiltration in the H pylori positive mucosa, but when biopsy specimens with equivalent neutrophil infiltration could be compared directly, positive specimens gave greater chemiluminescence than negative. Smoking, drugs, and alcohol consumption had no independent effect. It is concluded that excess mucosal reactive oxygen metabolite production is associated with H pylori gastric antral infection and may be an important pathogenic mechanism. There is no evidence for reactive oxygen metabolite participation in the pathogenesis of gastric mucosal injury in cases unrelated to H pylori infection.