The association between levels of alpha-tocopherol and selenium in serum and subsequent risk of gastrointestinal cancer was investigated in a longitudinal study based on 36,265 Finnish men and women, aged 15-99 and initially free of cancer. Serum alpha-tocopherol and serum selenium levels at entry into the study were measured from stored serum samples of 150 incident gastrointestinal cancer cases diagnosed during a follow-up of 6-10 years and for 276 controls who were matched for sex, age and place of residence. Subjects with a low level of alpha-tocopherol or selenium had an elevated subsequent risk of cancer of the upper gastrointestinal tract. This association persisted among men after adjustment for various confounding factors and after the exclusion of those with cancer diagnosed during the first 2 years of follow-up. The relative risk of cancer of the upper gastrointestinal tract among men who fell in the lowest quintile of serum selenium was 3.3 (95% confidence limits, 1.3 and 9.1) while among those who fell in the 3 lowest quintiles of alpha-tocopherol it was 2.2 (95% confidence limits 0.9 and 5.6) compared with those in the higher quintiles. Serum levels of selenium or alpha-tocopherol in general were not inversely associated with colorectal cancer risk. These findings indicate that high selenium intake and possibly also high vitamin E intake, especially among men, may provide protection against cancer of the upper gastrointestinal tract but not against colorectal cancer.