In plants and mammals, small RNAs indirectly mediate epigenetic inheritance by specifying cytosine methylation. We found that small RNAs themselves serve as vectors for epigenetic information. Crosses between Drosophila strains that differ in the presence of a particular transposon can produce sterile progeny, a phenomenon called hybrid dysgenesis. This phenotype manifests itself only if the transposon is paternally inherited, suggesting maternal transmission of a factor that maintains fertility. In both P-and I-element-mediated hybrid dysgenesis models, daughters show a markedly different content of Piwi-interacting RNAs (piRNAs) targeting each element, depending on their parents of origin. Such differences persist from fertilization through adulthood. This indicates that maternally deposited piRNAs are important for mounting an effective silencing response and that a lack of maternal piRNA inheritance underlies hybrid dysgenesis.In Drosophila melanogaster, the progeny of intercrosses between wild-caught males and laboratory-strain females are sterile because of defects in gametogenesis, whereas the genetically identical progeny of wild-caught females and laboratory-strain males remain fertile (1-3). This phenomenon, known as hybrid dysgenesis, was attributed to the mobilization in dysgenic progeny of P-element or I-element transposons, which were present in wild-caught flies but absent from laboratory strains (4-9). The disparity in outcomes, depending on the parent of transposon origin, indicated the existence of cytoplasmically inherited determinants of the phenotype, which must be transmitted through the maternal germ line (8,9).The control of mobile elements in germ cells depends heavily on a small RNA-based immune system, composed of Piwi-family proteins (Piwi, Aubergine, and AGO3) and piRNAs (10,11). Both Piwi and Aubergine (Aub) are deposited into developing oocytes and accumulate in the pole plasm (12,13), implying possible transfer of maternal piRNAs into the germ lines of their progeny. We therefore asked whether maternally deposited small RNAs might affect transposon suppression in a heritable fashion and whether piRNAs might be the maternal suppressor of hybrid dysgenesis.