The DNase I sensitivity of total chromatin has been analyzed in nuclei isolated from control and interferon-treated Daudi cells. The electrophoretic analysis of DNA has evidenced a different pattern of DNA fragment size produced by DNase I in nuclei isolated from control cells compared to interferon-treated samples. This feature is supported by a different recovery of acid soluble chromatin and is accompanied by modifications of in vitro RNA synthesis along with initiation and elongation of RNA chains. No changes have been evidenced in nuclei isolated from Daudi-resistant cells under the same experimental conditions. These data might be interpreted as a transient modulation, induced by interferon, of chromatin structure in terms of chromatin condensation which, in turn, activates the RNA synthesis after the transduction into the nucleus of the interferon-generated signals.