The classical theory on the solubility of ionic compounds has been extended to solid solutions and deviations from stoichiometry by combination of thermodynamical and solid state chemical principles. Theory predicts that the incorporation of foreign ions in enamel apatite can change its solubility product over several orders of magnitude in several ways. Experimental data on the composition of enamel indicate that the incorporation of F- ions will stabilize the enamel crystals by the apparent diminution of Na+ and CO32- incorporation. The additional effect may be that a change in the type of the main ternary apatite in enamel apatite crystals, carbonatoapatite into hydroxyapatite, is induced by incorporation of a relatively small amount of F- ions. It is estimated that these effects in combination lower the solubility product of enamel apatite, calculated as Koha, by 5–10 orders of magnitude. The present theory can be used to screen other single or combined substitutions for their possible anticariogenic effect. Kinetic factors determining the success of prevention by ion incorporation are discussed.