Globin gene expression, which occurs exclusively in the erythroid cell lineage, is controlled at the level of transcription. It is thus of some considerable interest to compare the chromatin structure of this gene with that of inactive genes in erythroid cell nuclei and to compare the chromatin structure of the globin gene in its active and inactive states in nuclei of different cell types. Other workers have observed that globin genes in erythroid cell nuclei exhibit the enhanced overall sensitivity to nucleases and the hypersensitive site in the 5'-flanking sequence typical of many active genes. The nature of the structural changes giving rise to nuclease sensitivity are however obscure. We have investigated the local higher order structure of chromatin in the region of unique genes in chicken by sucrose gradient sedimentation of chromatin restriction fragments. We find that ovalbumin and alpha 2-collagen gene fragments in erythrocyte chromatin and an adult beta-globin gene fragment in spleen chromatin sediment with bulk chromatin fragments of the same DNA size, whereas the beta-globin gene fragment in erythrocyte chromatin sediments more slowly than bulk fragments of equivalent size. The simplest interpretation of the results is that the solenoid structure in the region of the globin gene is selectively and permanently unfolded on gene activation.