The salt-induced folding and self-association of histone H4 and its fragments (1-23), (25-67), (69-84), and (69-102) have been studied at the same molar concentration (1 mM) by nuclear magnetic resonance (NMR), circular dichroism (CD), and ir spectroscopy. Byeach of these techniques intact histone H4 exhibited a fast structural change, involving the formation of alphaR helix and aggregation, and also a slow change involving beta-structure formation. Fragment (25-67) was found to behave in a manner similar to the intact molecule for the fast change, showing both helix formation and aggregation but exhibited no time-dependent effects. All the other fragments were found to be essentially noninteracting. It is concluded that (25-67) contains the rgion critical for the folding and self-association of histone H4. On the basis of these results a model is proposed for the self-association of histone H4 in which helix is located between residues 49 and 73, while the beta structure lies between 74 and the C-terminus.