A selenocysteine-containing rat plasma protein (selenoprotein P) was examined for a possible role in the transport of selenium in the rat. A time-course study of the localization of injected 75Se from [75Se]selenite indicated that one-half of the selenium was sequestered by liver tissue 1 h after injection and that one-fourth of the 75Se in the plasma was attached to selenoprotein P 3 h after injections. By 25 h there was little 75Se in plasma, and much of the 75Se had accumulated in nonhepatic tissues. 75Se was incorporated into selenoprotein P by liver slices in a process that was sensitive to the protein synthesis inhibitor cycloheximide. The fate of 75Se from intracardially injected 75Se-labeled selenoprotein P was followed in rats maintained on selenium-deficient and selenium-sufficient diets. Substantially more of the injected 75Se was present per gram wet weight in the testes and kidneys than the livers of the selenium-deprived rats after 5 h. The results indicate that selenoprotein P is synthesized in rat liver and that it transfers selenium from the liver to extrahepatic tissues.