Drosophila simulans and Drosophila mauritiana are sibling species that show substantial sexual isolation in one of their two reciprocal hybridizations. Genetic analysis reveals that in females this isolation is caused by at least one recessive gene on each autosome, while the X chromosome has little or no effect. Our results, combined with those of previous studies, show that in Drosophila the genetics of sexual isolation differs from that of postzygotic reproductive isolation, which invariably involves large effects of the X chromosome.