Reproductive isolation leads to the evolution of new species (speciation) and is mediated by two factors: hybrid sterility and hybrid inviability, which have different causes. Hybrid inviability can be explained by the "dominance theory" in which genes that cause it will be expressed in the heterogametic (XY) sex while remaining masked in the homogametic (XX) sex. The situation in hybrid sterility is less clear, but recessive factors and faster male evolution both contribute to the pattern seen for hybrid sterility. The identification of genetic factors leading to inviability or sterility has been hampered by the fact that, by definition, crossbreeding to analyze genetic effects cannot occur. However, rescue mutations that lessen these effects have recently been isolated, allowing the full range of Drosophila genetics to be exploited. In the June 12 Nature, Daven Presgraves and colleagues at the University of Rochester have adopted such an approach and describe a mechanism by which a single gene encoding two nuclear pore proteins can cause hybrid inviability (Nature, 423:715-719, June 12, 2003).