In Drosophila position effect variegation and Polycomb-dependent regulation of homeotic gene expression are phenomena in which genes are inactivated in a clonally inherited manner. In both processes inactivation involves proteins that interact with the chromosome at or close to the position of inactivated genes. Two models have been proposed to explain this form of genetic silencing. In one, cooperative concatamerisation of a large multisubunit protein complex packages the chromatin fibre into a higher order structure, which is inaccessible for the transcription apparatus. In the second, the chromatin fibre is left unaltered but the region to be silenced is assigned to a compartment within the nucleus to which not all transcription factors have access. To distinguish between these types of model we have used the ligation-mediated PCR procedure to quantitate the accessibility of restriction sites in the chromatin fibre in both the active and inactivated forms. By making use of appropriate mutations and tissues we show that the inactivation of genes by Polycomb or by position effect variegation is not accompanied by a substantial change in the accessibility of the fibre. These results favour models in which the inactivation is achieved by sequestration of the silenced region in a particular nuclear compartment rather than by a chromatin packaging model.