In the crowded intranuclear environment, entropic depletion forces between macromolecules are expected to be strong. A review of simulations of linear polymers leads to several predictions about probable conformations of a polynucleosome chain in these conditions. These include a globular conformation, variable compaction due to different local rigidity or curvature of the mosaic of isochores, satellite sequences, and nucleosomes containing different histone variants, and the possibility that chromosomes represent separate phases like those seen in heterogeneous particle mixtures by experiment and simulation. Experimental results which show that macromolecular crowding alone, in the absence of exogenous cations, can stabilise interphase chromosomes and cause self-association of polynucleosome chains are presented. Together, these considerations suggest that macromolecular crowding and entropic forces are major factors in packing polynucleosome chains in vivo.