Escherichia coli adapts to changes in growth osmolarity of at least 100-fold by making large changes in the amounts of intracellular water and solutes, including cytoplasmic K+. A wide range of in vitro salt, solute and biopolymer concentrations should therefore be considered 'physiological'. Paradoxically, these large, osmotically induced changes in cytoplasmic K+ concentration do not greatly affect the equilibria and kinetics of cytoplasmic protein-nucleic acid interactions. Biophysical effects resulting from changes in the amount of cytoplasmic water (such as macromolecular crowding) and in the concentrations of other cytoplasmic solutes appear to compensate for the effects of changes in cytoplasmic K+ concentration and thereby maintain protein-nucleic acid equilibria and kinetics in the range required for in vivo function.