A physical model of selective “ion binding” in the L-type calcium channel is constructed, and consequences of the model are compared with experimental data. This reduced model treats only ions and the carboxylate oxygens of the EEEE locus explicitly and restricts interactions to hard-core repulsion and ion–ion and ion–dielectric electrostatic forces. The structural atoms provide a flexible environment for passing cations, thus resulting in a self-organized induced-fit model of the selectivity filter. Experimental conditions involving binary mixtures of alkali and/or alkaline earth metal ions are computed using equilibrium Monte Carlo simulations in the grand canonical ensemble. The model pore rejects alkali metal ions in the presence of biological concentrations of Ca 2+ and predicts the blockade of alkali metal ion currents by micromolar Ca 2+. Conductance patterns observed in varied mixtures containing Na + and Li +, or Ba 2+ and Ca 2+, are predicted. Ca 2+ is substantially more potent in blocking Na + current than Ba 2+. In apparent contrast to experiments using buffered Ca 2+ solutions, the predicted potency of Ca 2+ in blocking alkali metal ion currents depends on the species and concentration of the alkali metal ion, as is expected if these ions compete with Ca 2+ for the pore. These experiments depend on the problematic estimation of Ca 2+ activity in solutions buffered for Ca 2+ and pH in a varying background of bulk salt. Simulations of Ca 2+ distribution with the model pore bathed in solutions containing a varied amount of Li + reveal a “barrier and well” pattern. The entry/exit barrier for Ca 2+ is strongly modulated by the Li + concentration of the bath, suggesting a physical explanation for observed kinetic phenomena. Our simulations show that the selectivity of L-type calcium channels can arise from an interplay of electrostatic and hard-core repulsion forces among ions and a few crucial channel atoms. The reduced system selects for the cation that delivers the largest charge in the smallest ion volume.