The study provides data relating serum selenium concentration to activities of 2 key selenoenzymes, hemolysate thioredoxin reductase (TR) and glutathione peroxidase (GPx), measured by spectrophotometry, in a group of men at high risk for prostate cancer. This trial enrolled 43 patients with elevated prostate-specific antigen but negative biopsy for prostate cancer. Such individuals have a high risk of developing prostate cancer in the succeeding 5 y. In the men with baseline serum selenium concentrations ranging from 0.74-1.62 micromol/L (59-128 microg/L), hemolysate TR (r = 0.359, P < 0.05) and GPx (r = 0.341, P < 0.05) activities increased with increasing serum selenium. Furthermore, after a run-in period of 1 mo, men participated in a randomized, double-blind, placebo-controlled selenium supplementation trial for 6 mo and received a placebo, or 200 or 400 microg of Se per day, in the form of a seleno yeast. This study is a subsidiary of an ongoing Phase III cancer chemoprevention trial and, as such, randomization groups have not yet been revealed. After 6 mo of being on trial and with an estimated 66% of the group being supplemented with seleno yeast, the TR activity of the group increased by 80% relative to baseline. In contrast, 6 mo of selenium supplementation did not affect GPx activity. This study presents, to our knowledge for the first time, both measurements of human hemolysate TR activity and its relation to serum selenium.