Based on studies of histone acetylation in vivo in Physarum polycephalum, we present the following hypotheses: (1) Transcription-specific histone acetylation on histones H3 and H4 is a localized process at the nuclear matrix; (2) Histone acetylation in the S phase, which is specific for newly synthesized histones, occurs in an intranuclear nonlocalized process. These hypotheses can explain: (1) the histone specificity of histone acetylation that is dependent on the functional state of the chromatin; (2) the apparent absence of turnover of histone acetylation in the bulk of the chromatin despite a definite low level of steady-state acetylation of all four core histones in bulk chromatin; (3) the pattern of butyrate-induced hyperacetylation observed for active and inactive chromatin.