We have analyzed the RNA synthetic activity in intact HTC cells which have artificially high or low levels of histone acetylation. Rates of total RNA synthesis and the number of nascent transcription complexes have been measured for 20-h butyrate-treated cells and for butyrate-released cells which contain hypoacetylated histones. Exposure of HTC cells to butyrate for 20 h leads to a approximately 40% decrease in the number of nascent RNA molecules and a corresponding approximately 40% decrease in the rate of total RNA synthesis. During the induction of hypoacetylation following the release of cells from butyrate, rates of RNA synthesis and the number of nascent transcripts remain unchanged. Between the fifth and eighth h of release from butyrate, the number of nascent transcripts and the rate of total RNA synthesis increase to control cell levels. This increase in the number of nascent RNA polymerase complexes, while occurring when bulk histone is hypoacetylated, is temporally correlated with an increase in the rate of acetylation for a subset of histones. In contrast, changes in levels and rates of histone acetylation were found to be without effect on the average rate of RNA chain elongation. Additionally, we have found that the complexity of nuclear RNA is unchanged by a 20-h exposure of HTC cells to butyrate, suggesting that the approximately 40% decrease in frequency of nascent polymerase complexes produced by butyrate does not result from the complete loss of transcription of a large number of genes.