Studies of population genetics have been almost exclusively confined to theory and surveys of polymorphism in natural populations. Experiments in evolution have been extremely difficult to perform in a rigorous manner because established transgenic technology in most higher eukaryotes is unsuitable for such studies. Recent advances in gene knock out and transgene co-placement in Drosophila melanogaster remove most of the obstacles. We would like to put these methods together into a comprehensive framework and apply them to the study of reproductive isolation between behavioral races of D. melanogaster. Lessons learned from our experiments could then be applied to studies of complex genetic traits in other organisms. For example, many human genetic deseases, such as cancer susceptibility, are influenced by many genes.