A powerful way to map functional genomic variation and reveal the genetic basis of local adaptation is to associate allele frequency across the genome with environmental conditions. Serpentine soils, characterized by high heavy-metal content and low calcium-to-magnesium ratios, are a classic context for studying adaptation of plants to local soil conditions. To investigate whether Arabidopsis lyrata is locally adapted to serpentine soil, and to map the polymorphisms responsible for such adaptation, we pooled DNA from individuals from serpentine and nonserpentine soils and sequenced each 'gene pool' with the Illumina Genome Analyzer. The polymorphisms that are most strongly associated with soil type are enriched at heavy-metal detoxification and calcium and magnesium transport loci, providing numerous candidate mutations for serpentine adaptation. Sequencing of three candidate loci in the European subspecies of A. lyrata indicates parallel differentiation of the same polymorphism at one locus, confirming ecological adaptation, and different polymorphisms at two other loci, which may indicate convergent evolution.