How similar are mouse embryonic stem (ES) cells to the early embryonic cells they are derived from? On p. 3215, Jennifer Nichols and colleagues now show that both cell types are inherently pluripotent and that signals in the early embryo induce differentiation rather than actively maintain pluripotency. Recent advances in ES cell derivation -involving Gsk3 kinase and Erk kinase pathway inhibition - sparked the idea that epiblast cells from the embryonic inner cell mass (ICM), which normally differentiates into both hypoblast and epiblast, might possess an ES cell-like state that is maintained when inductive signals are inhibited. The authors investigated the effect of such inhibition on early mouse embryonic development and found that it causes the ICM to express the epiblast marker Nanog throughout, indicating that the hypoblast is lost. Like normal epiblast,the Nanog-expressing ICM cells give rise to ES cell clones and can be used to generate chimaeric animals. Thus, the authors propose, embryonic epiblast and cultured ES cells possess essentially the same inherent pluripotency.