Binding of di- or polyvalent cations is necessary to maintain the chromatin in isolated nuclei and metaphase chromosomes in a condensed state. We here show that the native, porous structure of the heterochromatin in the interphase nucleus requires both K+ and Mg2+ in concentrations, which are known to support transcription in isolated nuclei, thus providing a functional state of the chromatin. When these cations are acting separately, the chromatin is more condensed by Mg2+ and decondensed by K+. Comparison with published values of the free electrostatic energy of DNA in chromatin shows that this state of compaction is the result of a balance between the different aggregative properties of K+ and Mg2+ at a high degree of charge shielding. (C) 2004 Elsevier Inc. All rights reserved.