Acquired epigenetic modifications, such as DNA methylation or stable chromatin structures, are not normally thought to be inherited through the germline to future generations in mammals [1] [2]. Studies in the mouse have shown that specific manipulations of early embryos, such as nuclear transplantation, can result in altered patterns of gene expression and induce phenotypic alterations at later stages of development [3] [4] [5]. These effects are consistent with acquired epigenetic modifications that are somatically heritable, such as DNA methylation. Repression and DNA methylation of genes encoding major urinary proteins, repression of the gene encoding olfactory marker protein, and reduced body weight can be experimentally induced by nuclear transplantation in early embryos [4]. Strikingly, we now report that these acquired phenotypes are transmitted to most of the offspring of manipulated parent mice. This is the first demonstration of epigenetic inheritance of specific alterations of gene expression through the germline. These observations establish a mammalian model for transgenerational effects that are important for humal health, and also raise the question of the evolutionary importance of epigenetic inheritance.