Study of the structural organization of chromatin during transcription and replication may reveal important aspects of these processes. At the lowest level of organization, chromatin consists of a repeating subunit, the nucleosome (for reviews see refs 1-3). Electron microscopy indicates that the nucleosomes are arranged helically or form discrete superbeads, generating the familiar 250 A-300-A fibre. It has been suggested that this fibre is further folded into loops containing up to several hundred nucleosomes. Despite extensive study, the significance and fate of these nucleosomes remain obscure. We have used here micrococcal nuclease digestion to compare the structures of actively transcribing and inert chromatin of the genes coding for the major heat-shock protein of Drosophila melanogaster. The repressed hsp 70 genes were considerably more resistant to cleavage by micrococcal nuclease than their flanking regions and the bulk of chromatin. The active genes, previously shown to be more sensitive than the repressed genes, are also more susceptible to the nuclease than their 3'-flanking regions and bulk chromatin.