OBJECTIVE To investigate whether duodenal ulcer (DU) is associated with increased free radical generation at the site of ulceration and to attempt, indirectly, to confirm the hypothesis by determining activity of free radical scavengers such as superoxide dismutase (SOD). METHODS Prospective study comparing SOD activity in biopsies taken from the ulcer edge, and antrum in DU patients before and after one month of treatment to SOD activity in biopsies from the duodenal bulb and antrum in a control population. METHODS Institute of Gastroenterology of a university hospital. METHODS Twenty-five patients with DU. The diagnosis was confirmed by endoscopy. METHODS SOD activity in biopsy specimen, red blood cells (RBC) and serum was measured using the cytochrome c method by spectrophotometry and expressed as U SOD/mg protein. Helicobacter pylori was diagnosed by the rapid urease test (CLO test) from antral biopsies. RESULTS SOD activity was markedly depleted in the ulcer edge (2.78 +/- 0.9 U SOD/mg protein) as compared to the same patients after one month of treatment (4.59 +/- 2.2 U SOD/mg protein) (P = 0.05) and to biopsies from the duodenal bulb in control population (6.7 +/- 2.4 U.SOD/mg protein) (P = 0.05). SOD activity in the antrum of both groups was similar. There was no difference in SOD activity in RBC and serum of both groups. CONCLUSIONS Products of free radical reactions are implicated in the pathogenesis of DU disease. SOD, which is a key enzyme in gastric mucosal protection, is depleted significantly in the ulcer edge compared with controls and increases after healing. However, it is not clear whether this abnormality in oxygen free radical metabolism reflects, rather than causes, the condition which characterizes DU.