The involvement of post-transcriptional mechanisms in the determination of the frequency distribution of messenger RNA sequences has been studied in cloned mouse embryo cells in culture. Hybridization kinetic experiments between poly(A)-containing RNA and complementary DNA have been used to study the alterations in frequencies which occur in those nuclear poly(A)-containing RNA sequences which are conserved in cytoplasmic poly-ribosomes. Sequences adjacent to nuclear poly(A) tracts are present in a much narrower frequency distribution in the nucleus than in polysomes, with a large proportion of the nuclear sequences present in an average frequency of about one molecule per cell. Few nuclear sequences appear to be present in more than ten copies per cell. A minimum of 70% of these sequences are also found in poly-ribosomal RNA but in greatly altered frequencies. Abundant sequences which comprise a major fraction of the poly(A)-containing polyribosomal RNA are derived from a small fraction of the nuclear poly(A)-adjacent RNA sequences. Very few nuclear poly(A)-adjacent sequences are present in a frequency characteristic of high abundance polysomal sequences. Conversely, poly(A)-containing polyribosomal RNA appears to contain few sequences which are present in as low a frequency as the majority of nuclear poly(A)-adjacent sequences. These observations suggest that post-transcriptional mechanisms play a major role in determining the steady-state frequency of polyribosome-associated messenger RNAs.