The hyperacetylation of histones due to treatment of cultured cells with sodium butyrate has been studied. The hyperacetylation is due to inhibition of histone deacetylase. Other short chain fatty acids including acetic, isobutyric and propionic acid also produce increased modification. Histone H4 already deposited on the chromosome can be rapidly acetylated to the extent of about 70%. That 80% of histone H4 is acetylated after a 24 hr exposure to butyrate is due to the fact that incoming H4 histone is 100% acetylated and does not return to the parental unmodified form in the presence of butyrate.