The hydroxyl radical is the most potent free radical derived from oxygen, and has been implicated in damage caused to the gastroduodenal mucosa. The ability of human gastric juice to generate hydroxyl radicals has been investigated in 54 adults with endoscopically normal gastroduodenal mucosa and in 39 patients with chronic duodenal ulcer. Hydroxyl radical production was measured by the formation of formaldehyde from dimethylsulfoxide. Unlike other body fluids, this reaction could proceed without the extraneous addition of catalysts such as hydrogen peroxide (H2O2), ascorbate and iron. Measurement of H2O2, iron and ascorbate showed that these catalysts are already present in the gastric juice. There was no significant difference in the concentration of these components in gastric juice between normal subjects and patients with duodenal ulcer, except that H2O2 levels were slightly higher in duodenal ulcer patients. Although generation of free radicals has been investigated in other body fluids, this is the first reported case regarding the production of these active species in normal human gastric juice. Since hydroxyl production is not significantly enhanced in duodenal ulcer, we suggest that attention may be turned to mucosal antioxidant defences in this disease.