Chaotropic agents are cosolutes that can disrupt the hydrogen bonding network between water molecules and reduce the stability of the native state of proteins by weakening the hydrophobic effect. In this work, we represent the chaotropic agent as a factor that reduces the amount of order in the structures formed by water molecules, both in the bulk and the hydration shells around hydrophobic amino acids. In this framework we show that low chaotrope concentrations lead to a destabilization of the native state of proteins, and that high concentrations induce complete denaturation. We also find that the reduction of the number of bulk ordered states of water molecules can give origin to an effective interaction between chaotropic molecules and proteins. Proteins 2005;61:492-499. (c) 2005 Wiley-Liss, Inc.