In view of various reports describing differences in histone acetylation between normal rat liver and hepatomas, the behaviour of histone acetyltransferase (EC 2.3.1.48) activity was elucidated in normal rat liver and in a spectrum of well-characterized rat hepatomas of slow, intermediate and rapid growth rates. In all tumours the acetyltransferase specific activity, expressed as nmol h-1 mg total protein-1, was higher than in the corresponding normal livers and the rise correlated positively with the proliferation rates of the tumors. No difference is observed if acetyltransferase activity is expressed per milligram of histone. This is explained by elevated ratios of histones and of DNA to total protein in the hepatomas compared to the ratios in normal liver. Electrophoretic analysis of [3H]acetate-labeled histones revealed similar patterns in hepatoma and normal liver. The extent of histone H4 acetylation, as indicated by the frequency distribution of non-, mono-, di-, tri-, and tetraacetylated H4-species, was found to be identical in hepatomas and normal liver. The histone protein and acetate labeling patterns were near normal in the slowly growing hepatomas.