The expression of the genes for several histones and pA-globin was examined in the chicken erythroid cell lineage. During the transition from CFU-(E) to the mature erythrocyte, histone H5 gradually increased fourfold in nuclei with little concomitant displacement of the Hi histones. This resulted in a 70% net increase in linker histone (Hi plus H5) content. The differential accumulation of H5 reflected (i) an increase in the transcriptional activity of the H5 gene occurring at the erythroblast stage, (ii) an apparent longer half-life of H5 mRNA, and (iii) a higher stability of the protein. Although the transcriptional activity of the histone genes (except H5) decreased with cell age, it was not tightly coupled to the S phase. On the other hand, the mRNA levels for these histones were tightly regulated during the cell cycle. Use of protein and DNA synthesis inhibitors indicated that the content of H5 mRNA was regulated at the posttranscriptional level by a control mechanism(s) differing from those for the other histones. Although the transcription rates of the H5 and pA_globin genes were comparable, differential accumulation of iA_globin mRNA led to a 30-to 170-fold-higher copy number of the pA-globin mRNA as the cell matured.