Experiments and molecular dynamics calculations have shown that cavitand I has a bimodal selectivity for alkali ions in water saturated CHCl3 (experiment) and water (simulations). In this paper, molecular dynamics and free energy perturbation calculations are used to study the selectivity of I for alkali ions in methanol. The calculations predict that Cs+ is bound tightest by I, the same as in water. As previously predicted, the bimodal selectivity disappears in methanol. This change in specificity is caused by a change in the number of stabilizing interactions in which solvent molecules that accompany the alkali ion into the cavity of I can participate.