Plant tolerance of serpentine soils is potentially an excellent model for studying the genetics of adaptive variation in natural populations. A large-scale viability screen of Arabidopsis thaliana mutants on a defined nutrient solution with a low Ca2+ : Mg2+ ratio (1 : 24 mol : mol), typical of serpentine soils, yielded survivors with null alleles of the tonoplast calcium-proton antiporter CAX1. cax1 mutants have most of the phenotypes associated with tolerance to serpentine soils, including survival in solutions with a low Ca2+ : Mg2+ ratio; requirement for a high concentration of Mg2+ for maximum growth; reduced leaf tissue concentration of Mg2+; and poor growth performance on `normal' levels of Ca2+ and Mg2+. A physiological model is proposed to explain how loss-of-function cax1 mutations could produce all these phenotypes characteristic of plants adapted to serpentine soils, why `normal' plants are unable to survive on serpentine soil, and why serpentine-adapted plants are unable to compete on `normal' soils.