Technical Abstract: Selenium (Se) is known to regulate tumorigenesis and immunity at nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8+ and CD4+ T cells, we asked whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na2SeO4) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 x 106 cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se- or Se++ diet, and the CD4+ T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4+ or CD8+ T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25+CD4+ T cells on Day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4+, but not CD8+ T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.