Single nucleotide polymorphisms, or SNPs, are the most prevalent form of genetic variation, and have been found to be associated with a number of human diseases. Efficient strategies to screen genomic DNA for specific mutations are essential for the burgeoning efforts to track SNPs in large populations. Using semiconductor microchips as their platform, Gilles and colleagues have developed a rapid and sensitive method for the discrimination of a complex quadra-allelic locus in a gene linked to immunosuppression in pediatric patients (see p. 365).