The effect of beta-carotene and DL-alpha-tocopheryl acetate (alpha-TAc) on the activity of ornithine decarboxylase (ODC) in human atrophic stomach mucosa and intestinal metaplasia (IM) was studied in a double-blind intervention trial. Persons (227) with upper gastrointestinal symptoms and/or atrophic gastritis (AG) were examined. It was found that ODC activity in the biopsies of antral mucosa increased gradually from normal mucosa (7.2 +/- 1.8 units) to superficial gastritis (22.7 +/- 5.9 units) and to AG (54.2 +/- 6.9 units). Enzyme activity in cases of IM did not differ from atrophic mucosa without IM (56.1 +/- 8.0 versus 51.4 +/- 5.6 units; P > 0.05). For the intervention trial, 3 groups of 20 patients with AG were studied. Patients were supplemented daily for 1 year with beta-C (20 mg; group 1), alpha-TAc (55 mg; group 2), or placebo (group 3). No significant change in ODC activity was observed in placebo-treated subjects during 1-year follow-up. During the first 3 months, beta-C supplementation resulted in about a 50% decrease in ODC activity in atrophic mucosa. A moderate decrease in ODC activity of approximately 18% was observed after 6 months supplementation with alpha-TAc. The possible role of ODC in gastric carcinogenesis is discussed.