Selenium is readily absorbed from the gastrointestinal tract and utilized for synthesis of selenoproteins. Roles of intestine, liver, and selenoprotein P in this process were evaluated. Rats were given 75Se-selenite by stomach tube, and distribution of 75Se was followed for 3 h. A high portal vein plasma-to-hepatic vein plasma ratio of 75Se 15 min after 75Se administration and earlier uptake by liver than by other tissues indicated avid hepatic extraction of absorbed selenium from portal vein blood. The results of gel filtration of plasma taken 15 min after 75Se administration suggested that the 75Se was in the form of small molecules with some affinity for protein. Immunoprecipitation studies using plasma indicated that 75Se began to appear in selenoprotein P between 15 and 30 min after intragastric administration. To evaluate the role of the liver in the fate of absorbed selenium, rats with portacaval shunts, in which absorbed selenium bypasses the liver, were compared with sham-operated rats. After intragastric administration of selenium, uptake by the liver and incorporation into selenoprotein P were diminished in rats with portacaval shunts but kidney uptake and urinary excretion were increased. This suggests that hepatic extraction of absorbed selenium from portal vein blood decreases its entrance into the systemic circulation. The results of this study indicate that intestine releases absorbed selenium into portal blood in a small-molecule form, designated A-Se, which is highly extracted by the liver. The liver takes up A-Se better than other tissues because of a high extraction capacity and the fact that it is the first organ through which the blood from the intestine passes.