It has been shown that T3 administration to thyroidectomized rats induces a marked increase of the in vivo labelling of liver nuclear RNA by 6-[14C]-orotic acid and, although to a lesser extent, of the radioactivity of the acid-soluble fraction. Therefore, in evaluating the real increase in RNA synthesis induced by T3 administration it has been taken into account that the hormone stimulates the uptake of the labelled precursor by the liver and enhances the specific activity of the nucleoside and nucleotide pool. The greater penetration of orotate into the liver does not depend on the increased RNA synthesis since it is not prevented by the administration of actinomycin D which markedly inhibits the transcriptional process. These findings indicate that the increased uptake of orotate and the stimulation of RNA synthesis represent distinct effects of the thyroid hormone on its target tissue.