The authors examined the associations between dietary factors and the risk of duodenal ulcer in a prospective cohort of 47,806 men, aged 40-75 years, who were free of diagnosed gastric or duodenal ulcer or cancer. During 6 years of follow-up, they documented 138 newly diagnosed cases of duodenal ulcer. They found little evidence for an important effect of fat, type of fat, or protein intake. Higher consumption of fruits and vegetables was associated with lower risk of duodenal ulcer (relative risk (RR) = 0.67, 95% confidence interval (CI) 0.39-1.15 for > or = 7 servings per day vs. < 3 servings per day) after adjustment for age, body mass index, smoking, and use of aspirin or other nonsteroidal anti-inflammatory drugs. Total dietary fiber intake was inversely associated with the risk of duodenal ulcer (RR = 0.55, 95% CI 0.31-0.96 for men in the highest vs. the lowest quintile of dietary fiber). The soluble component of fiber was strongly associated with a decreased risk of duodenal ulcer (RR = 0.40, 95% CI 0.22-0.74 for the highest quintile). Several age- and energy-adjusted nutrients correlated with dietary fiber were also inversely related to the risk of duodenal ulcer, but vitamin A from all sources combined (including supplements and multivitamins) was the only nutrient that was statistically significant after adjustment for other risk factors (RR = 0.46, 95% CI 0.23-0.91 for men in the highest vs. the lowest quintile of vitamin A intake). These findings provide evidence that vitamin A from all sources, as well as diets high in fruits and vegetables, may reduce the development of duodenal ulcer, possibly due to their fiber content. Although the associations appeared stronger for dietary fiber and vitamin A, the authors can not exclude the possibility that other closely correlated dietary factors may be the true protective factors.