Patients with advanced cancer exhibit multifaceted defects in their immune capacity, which are likely to contribute to an increased susceptibility to infections and disease progression and to constitute a barrier to immunotherapeutic interventions. A chronic inflammatory condition associated with increased oxidative stress has been suggested as one of the responsible mechanisms behind the tumor-induced immune suppression. We, therefore, speculated that supplementation with the antioxidant vitamin E could enhance the immune functions in patients with advanced cancer. This hypothesis was here tested in twelve patients with colorectal cancer (Dukes' C and D) who, prior to intervention with chemo- or radiotherapy, received a daily dose of 750 mg of vitamin E during a period of 2 weeks. Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation, as compared with peripheral blood monocyte samples taken before treatment (P = 0.02). Interestingly, there seemed to be a more pronounced stimulatory effect by vitamin E on naïve (CD45RA(+)) T helper cells as compared with T cells with a memory/activated phenotype. Dietary vitamin E may be used to improve the immune functions in patients with advanced cancer, as a supplement to more specific immune interventions.