Mouse embryonic stem (ES) cells are the in vitro counterparts of the epiblast cells of the early postimplantation embryo. ES cells are highly pluripotent-they can generate all cell types of the adult organism, which reflects the central role of the epiblast as the founder tissue of the whole embryo in rodents. Mouse ES cells display unusual proliferative properties: their derivation does not rely on any immortalizing agent; they cannot enter a quiescence state; they do not undergo senescence; and they can proliferate without apparent limit. They also can multiply in the absence of serum and are not subject to contact inhibition or anchorage dependence. Human ES cells are also immortal and can form tumors in vivo, suggesting that, besides pluripotency, infinite life span and unrestricted growth are intrinsic features of all ES cells. Some fundamental differences in the expression or regulation of cell-cycle control genes-more specifically, in those regulating the G1-S transition in response to mitogenic signals-are likely to underlie the growth properties of mouse ES cells. In the G1 phase, retinoblastoma (RB) is sequentially phosphorylated by complexes of cyclins and cyclin-dependent kinases (CDKs). The lack of control over the G1-S transition in ES cells-and the gain of this control during differentiation-is likely to reflect a similar phenomenon in the early postimplantation embryo. Epiblast cells are highly proliferating and potentially tumorigenic. The onset of gastrulation is associated with an increase in the proliferation rate of epiblast cells as well as with the start of differentiation within the embryo proper.