Selenium (Se) is an essential nutritional factor that was shown by us to alter the expression of the high affinity interleukin 2 receptor (Il2-R) and its subunits, cell proliferation, and clonal expansion of cytotoxic T-lymphocytes in mice. This study shows that dietary supplementation of Se-replete humans with 200 micrograms/d of sodium selenite for 8 wk, or in vitro supplementation with 1 x 10(-7) M Se (as sodium selenite), result in a significant augmentation of the ability of peripheral blood lymphocytes to respond to stimulation with 1 microgram/mL of phytohemagglutinin or alloantigen (mixed lymphocyte reaction) and to express high affinity Il2-R on their surface. There was a clear correlation between supplementation with Se and enhanced 3H-thymidine incorporation into nuclear DNA, preceded by enhanced expression of high affinity Il2-R. Supplementation with Se can apparently modulate T-lymphocyte mediated immune responses in humans that depend on signals generated by the interaction of interleukin 2 with Il2-R.