Animal thioredoxin reductase is a selenoprotein. In this study, thioredoxin reductase activities in liver, kidney, and brain have been compared in rats fed selenium-deficient and control diets for 14 weeks following weaning. Selenium deficiency caused a decrease in thioredoxin reductase activity from control to 4.5% in liver and 11% in kidney. However, brain thioredoxin reductase activity was not affected by selenium deficiency of this severity. Gold inhibited thioredoxin reductase activity in the liver in a manner typical of its effect on selenoenzymes. Repletion of selenium-deficient rats with injections of selenium caused thioredoxin reductase activity to increase more rapidly in the liver than glutathione peroxidase activity but more slowly than selenoprotein P. These results indicate that thioredoxin reductase activity in liver and kidney is sensitive to selenium nutritional status but that brain thioredoxin reductase activity is less sensitive.