Rates of histone acetylation and deacetylation in nuclei from fetal, adult, and two kinds of neoplastic rat hepatocytes were examined. Histone acetylation in isolated nuclei was measured in the presence of 6 mM sodium n-butyrate, a potent inhibitor of deacetylase, and in the absence of the inhibitor. The deacetylase activity was estimated from the difference between the rates with or without the inhibitor. Both histone acetylation and deacetylation in nuclei from hepatoma cells (AH 66 cells) occurred two times faster than those of nuclei from fetal and adult livers regardless of alpha-fetoprotein production. This increased acetylation and deacetylation in hepatoma cells may be ascribed to either the increased activities of the enzymes or the increased accessibility of histone to the enzymes in the chromatin. Autoradiographic analysis of acetylated histones showed that all of the internal histones of the nucleosomes were acetylated and that apparent difference was found in the pattern of acetylated fractions between hepatoma nuclei and normal liver cell nuclei.