OBJECTIVE: We examined the association between serum ferritin concentration and the risk of diabetes. RESEARCH DESIGN AND METHODS: We examined the cross-sectional associations among ferritin concentration, glucose tolerance status, and concentrations of insulin, glucose, and glycosylated hemoglobin in 9,486 U.S. adults aged > or = 20 years from the Third National Health and Nutrition Examination Survey (1988-1994). RESULTS: After adjusting for age, sex, ethnicity, education, BMI, alcohol consumption, alanine aminotransferase concentration, C-reactive protein concentration, and examination session attended, and after dichotomizing ferritin concentration into < 300 and > or = 300 micrograms/l for men and < 150 and > or = 150 micrograms/l for women, the odds ratios for newly diagnosed diabetes were 4.94 (95% CI 3.05-8.01) for men and 3.61 (2.01-6.48) for women. The increased risk of newly diagnosed diabetes was concentrated among participants with transferrin saturations < 45%. All multiple linear regression coefficients between ferritin concentration and concentrations of insulin, glucose, and glycosylated hemoglobin were positive and significant for both men and women. CONCLUSIONS: Elevated serum ferritin concentration was associated with an increased risk of diabetes. We were unable to eliminate conclusively the possibility that the observed association reflected inflammation rather than excess body iron stores.