The beta-globin and histone H5 genes are transcriptionally active in immature chicken erythrocytes and potentially active in mature erythrocytes. In both immature and mature erythrocytes, the majority of these erythroid-specific gene sequences are located in two chromatin fractions: the low-salt-insoluble residual nuclear material and the 0.15 M-NaCl-soluble oligo- and poly-nucleosomes. These salt-soluble chromatin fragments are enriched in hyperacetylated species of H4 and H2B, ubiquitinated and polyubiquitinated species of H2A and H2B and are depleted of linker histones H1 and H5. The competent, transcriptionally inactive embryonic epsilon-globin gene, which is part of the DNAase I-sensitive beta-globin domain, is highly enriched in the 0.15 M-NaCl-soluble polynucleosome fraction but not in the insoluble nuclear material. The repressed vitellogenin gene shows no enrichment in either of these fractions. These results suggest that only those genes that are expressed or have the potential for expression are enriched in the low-salt-insoluble nuclear material of immature or mature erythrocytes. The enrichment of active genes in the low-salt-insoluble residual nuclear material of immature erythrocytes is not dependent on on-going transcription, the presence of RNA or changes in the amount of acetylated histone species. Our results are consistent with the hypothesis that active and potentially active genes are insoluble because of the presence of preinitiation transcription complexes.