Clinical chemoresistance is a frequent complication of alkylating agent treatment of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors (e.g., sodium butyrate, NaBu) may increase target cell chemosensitivity. Apoptotic responses and expression of chromatin modifying enzymes in lymphoid cell lines. LP-1 and NCl-H929, to chlorambucil (CLB) and/or NaBu were examined in this study. NaBu augmented the apoptotic response in CLB-resistant LP-1 cells but antagonised it in CLB-sensitive NCl-H929 cells. CLB increased expression of methyltransferase I and histone acetyltransferase I in both cell lines while NaBu had only small effect. CLB-induced increased gene expression was attenuated by NaBu in CLB-sensitive NCl-H929 cells but not in resistant LP-1 cells. These results suggest that chromatin modifying agents may have differential effects on cells depending on their chemosensitivity. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.