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The relation between 5 classes of flavonoids (flavanones, flavan-3-ols, flavonols, flavones and anthocyanidines) and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in 3 areas of northern Italy. The study included 304 cases (275 men, 29 women) with a first diagnosis of squamous-cell carcinoma of the esophagus and 743 controls (593 men, 150 women) with no history of cancer, admitted for acute illnesses, unrelated to tobacco and alcohol consumption, to major hospitals of the areas under surveillance. Dietary habits were investigated using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed after allowance for age, sex, study centre, years of education, alcohol drinking, tobacco smoking, body mass index and energy intake. An inverse association emerged between flavanone intake and esophageal cancer risk (OR=0.38 for the highest vs. the lowest quintile, 95% CI=0.23-0.66). The inverse relation between flavanones and esophageal cancer tended to be stronger in those who drank >or=6 drinks/day. In conclusion, this study suggests that flavanone intake is inversely associated with esophageal cancer risk and may account, with vitamin C, for the protective effect of fruit, especially citrus fruit, on esophageal cancer.