As organisms are constantly exposed to many environmental stresses, dealing with stresses is an intrinsic protective mechanism to adapt oneself to the environment. Through exposure to milder stresses, animals increase stress resistance and viability, and thereby live longer. In Caenorhabditis elegans, it has been reported that exposure of adult worms to mild stresses can increase stress resistance. Recently, it has been becoming clear that the acquired stress resistance in the parental generation can be inherited to the next generation. However, the molecular mechanisms underlying the inheritance of acquired stress resistance remain largely unknown. Because endogenous small RNAs have been shown to play an important role in transgenerational epigenetic inheritance, we focused our attention on nuclear Argonaute proteins whose functions are essential for transcriptional regulation by endogenous small RNAs. We exposed larvae to hyperosmosis, and then measured the resistance to proteotoxity. Our measurements showed that exposure to hyperosmosis increased the stress resistance, and that the increased stress resistance in the parental generation was inherited to the offspring. We next knocked down each of the two nuclear Argonaute proteins, hrde-1 and nrde-3, in the parental generation. Either hrde-1 RNAi or nrde-3 RNAi resulted in suppression of the increased stress resistance in the offspring. Our results suggest that nuclear Argonaute proteins play a role in the transgenerational inheritance of acquired stress resistance. We are now examining underlying mechanisms in more detail.