It has been well documented that core and H1 histone mRNAs accumulate in a manner which closely parallels the initiation of DNA synthesis and histone protein synthesis, suggesting that the onset of histone gene expression early during S phase is at least in part transcriptionally mediated. In fact, it appears that throughout S phase the synthesis of histone proteins is modulated by the availability of histone mRNAs. On the other hand, the stability of histone mRNAs and the destabilization of histone mRNAs when DNA replication is completed or inhibited are highly selective, tightly coupled and largely post-transcriptionally controlled. We present a model to account for histone mRNA turnover whereby the natural or inhibitor-induced termination of DNA replication results in an immediate loss of high affinity binding sites for newly synthesized histone proteins which in turn brings about a transient accumulation of unbound histones. These unbound histones could modify the histone translation complex, via interactions with polysomal histone mRNAs, in such a manner as to render histone mRNAs accessible to cellular ribonucleases. This type of mechanism would be operative solely at the post-transcriptional level and would be compatible with the rapid, RNA synthesis-independent destabilization of histone mRNAs which occurs following inhibition of DNA replication, as well as with the requirement for protein synthesis for histone mRNA destabilization to be initiated.