The protective effects of alkali metal ions (Li+, Na+, K+, Rb+ and Cs+) against spermidine-induced DNA compaction were studied using single-molecule observations. We found that all alkali metal salts prevent DNA compaction, where Na+ more strongly prevented DNA compaction than other alkali metal ions. We discuss our results in terms of changes in ionic radii in relation to the net translational entropy of small ions due to ionic exchange between trivalent and monovalent cations. (c) 2006 Elsevier B.V. All rights reserved.