Ecologists have long sought mechanistic explanations for the patterns of plant distribution and endemism associated with serpentine soils. We conducted the first empirical test of the serpentine pathogen refuge hypothesis, which posits that the low levels of calcium found in serpentine soils provide associated plants with a refuge from attack by pathogens. We measured the range of soil calcium concentrations experienced by 16 wild population of California dwarf flax (Hesperolinon californicum) and experimentally recreated part of this range in the greenhouse by soaking serpentine soils in calcium chloride solutions of varying molarity. When flax plants grown in these soils were inoculated with spores of the rust fungus Melampsora lini we found a significant negative relationship between infection rates and soil calcium concentrations. This result refutes the pathogen refuge hypothesis and suggests that serpentine plants, by virtue of their association with low calcium soils, may be highly vulnerable to attack by pathogens. This interaction between plant nutrition and disease may in part explain demographic patterns associated with serpentine plant populations and suggests scenarios for the evolution of life history traits and the distribution of genetic resistance to infection in serpentine plant communities.