To test the validity of estimating age-related changes in rat liver nuclear RNA synthesis by following the incorporation of radioactive nucleotides into an acid-insoluble product, age-related changes in endogenous nucleotide concentration were investigated. Both the total nucleotide and the nucleoside monophosphate (NMP) concentration decreased as a function of age. Although NMP concentration decreased linearly from 6 months of age, total nucleotide concentration decreased in an exponential manner beginning at 2 months of age. These age-related changes in endogenous nucleotide pool concentration cannot, therefore, be due to changes in nuclear permeability alone but may also involve age-related changes in nuclear metabolism of endogenous nucleotides. Since nuclear functioning proteins must be synthesized in the cytoplasm and subsequently incorporated into the nucleus, the effect of age on the uptake and specific incorporation of several of these proteins involved in transcription was investigated. There was no age-related difference in either the rate of uptake or in the total amount of general cytosol proteins, histones, ribosomal proteins or RNA polymerase incorporated by rat liver nuclei in vitro.