Secondary lymphedema (LE) in the proximal extremities develop with relatively high frequency in cancer patients after tumor resection, lymph-node obliteration, and/or postoperative irradiation. Physical therapy combined with manual or mechanical lymph drainage and compression bandaging provides symptomatic relief but does prevent the progression of degenerative changes in the affected tissues. As biochemical studies have linked these changes significantly to the excessive generation of oxygen radicals in the affected tissues, LE therapy should aim to eliminate oxygen radical production. Because selenium is a functional component of antioxidant enzymes, has anti-inflammatory properties, and reduces the expression of endothelial cell adhesion molecules, its effect was investigated in postmastectomy patients with LE of the arm. Sodium selenite administered orally in isotonic solution (selenase) at oral dosages of 800 microg Se/day on days 1 through 4 and 500 microg Se/day on days 5 through 28 produced a spontaneous reduction in LE volume and normalized blood parameters in a manner consistent with diminished oxygen radical production. In a randomized, placebo-controlled, double-blind study with postmastectomy LE patients undergoing combined physical decongestion therapy (CPDT), selenite at similar dosages increased the efficacy of CPDT and improved the mobility and heat tolerance of the affected extremity. The patients in this study received 1000 microg of Se/day orally during the first week, 300 microg Se/day during the second and third weeks, and a maintenance dose of 100 microg Se/day during 3 months of follow-up. All patients remained erysipelas-free during the 3 weeks of CPDT and the 3-month follow-up period. Based on the available evidence, supplementation with sodium selenite in isotonic solution is judged to be a valuable and safe extension of the physical decongestive therapy of LE.