Cell membranes, which consist of a lipid bilayer, play a critical role in cellular bioactivities. The lipid bilayer interacts dynamically with water as well as ions. Membrane fluidity is lesser in ionic solutions than in pure water, although how ions reduce membrane fluidity has not yet been clarified. Here, we performed 4 x 100-ns molecular dynamics simulations of a POPE (1-palmitoyl-2-oleoyl-phosphatidylethanolamine [18:1]) lipid bilayer in the presence or absence of ions (NaCl, KCl, or CaCl2) and compared the systems to evaluate the influence of ions on the structural dynamics of membranes. Our simulation revealed that membrane fluidity (no ion-system > Ca-system > K-system > Na-system) did not correspond to the distribution or the direct binding of cations to lipids (Ca2+ > Na+ > K+). Interestingly, we found that the presence of cations induces dehydration of lipids. The number of cations in the interface region corresponded to the degree of lipid dehydration and the reduction in membrane fluidity (Na+ > K+ > Ca2+). We therefore propose that membrane fluidity is not affected by direct interactions between cations and lipids, but by the dehydration of lipid molecules in the presence of cations located adjacent to the membrane. (C) 2013 Elsevier B.V. All rights reserved.