During preimplantation development in mammals, most of the epigenetic marks in the genomes of the gametes are removed. Those on imprinted genes must be retained, however, in order to ensure expression of only the maternal or the paternal allele, and the correct growth of the embryo and placenta. On p. 3727, Mann and colleagues report that culturing preimplantation mouse embryos produces persistent alterations in the expression and methylation of several imprinted genes in the placenta, but leaves imprinted expression mostly unscathed in the embryo. Thus, for the imprinted genes H19, Ascl2, Snrpn, Peg3 and Xist, in vitro culture activates the normally silent allele only in placental tissues. For H19 and Snrpn, these expression changes are associated with decreased DNA methylation. The authors suggest that mechanisms to safeguard imprinting may be more robust in the embryo than in the placenta, and that these findings might aid the development of assisted reproductive technologies in humans, which sometimes produce offspring with imprinting disorders.