Objectives. To study the association of vitamin E status with occurrence of insulin-dependent diabetes mellitus (IDDM). Design. A case–control study nested within a 21-year follow-up study. Subjects. Nineteen incident IDDM patients with an average age of 28 years and three individually matched controls per patient. Main outcome measure. Serum concentrations of alpha-tocopherol. Results. Serum alpha-tocopherol concentration at the baseline examination was inversely associated with IDDM occurring 4–14 years later. The cholesterol-adjusted relative risk of IDDM between the highest and lowest thirds of the vitamin concentration was 0.12 (95% confidence interval = 0.02– 0.85). Conclusions. The finding corroborates the hypothesis of a protective effect of vitamin E against development of IDDM. Because of the relatively old age of the patients in the present population, further epidemiological studies on the topic are warranted.