The influence of solvent composition on equilibria in chiral ligand-exchange systems is explored by measuring protonation constants and equilibrium formation constants for all free species and complexes, respectively, in systems at 25 degreesC and an ionic strength of 0.1 M containing one of two classic chiral selector molecules (L-proline or L-hydroxy proline). the copper(II) ion, and an amino acid enantiomer. This set of thermodynamic constants is combined with multiple-chemical-equilibria theory to determine solution composition as a function of pH and mole-fraction methanol (MeOH) in the solvent. Results indicate that the addition of MeOH increases the stabilities of both the hetero- and the homo-chiral ternary complexes. However, it also increases, often to a greater extent, the stability of each bis binary complex. As a result, the influence of MeOH addition on equilibria in chiral ligand-exchange systems is complex acid cannot be predicted by mere inspection of the equilibrium constants for the hetero- and homo-chiral ternary complexes. These results therefore identify a potential limitation of using common global stoichiometric models to predict equilibria in chiral ligand-exchange systems. A more comprehensive model, based on the complete description of the multiple chemical equilibria, is proposed. Finally, the role of solvent in stabilizing ligand-exchange complexes is explored through a series of molecular mechanics simulations in the absence or presence of solvent molecules. Results suggest that solvent stabilizes both bis binary and ternary complexes, primarily through direct participation in the complex structure in the form of occupancy of one or both distal coordination sites.