"Systems Genetics" detects variation in phenotypic traits and integrates this with underlying genetic variation. A powerful application of systems genetics is analyzing effects of genome-wide genetic variants on transcriptome-wide variation in gene expression. We see systems genetics as a new powerful technology which will empower research in genetics and in other disciplines. Here, we present preliminary analyses of systems genetics approaches to defining genetic interactions within the thymus, which is the key site for T lymphocyte development and imposition of immunological tolerance.