In both experiment and molecular simulation, it is found that a higher pressure is required to sustain the infiltration of smaller ions in a molecular-sized nanochannel. Simulations indicate that the effective ion solubility of the infiltrated liquid is reduced to nearly zero. Because of the strong interactions between the ion couples and the solid or liquid phases, an external force is required to continuously advance the confined liquid segment. The competition between the probability of ion entry and ion-couple formation causes the observed ion-size-dependent characteristics. © 2009 The American Physical Society.