Despite the importance of germ cells to the survival of species, little is known about their embryological origin, proliferation, migration and entry into mitotic arrest or meiosis. We have studied the effect of Steel factor (c-kit ligand), LIF (leukemia inhibitory factor) and bFGF on cultured murine primordial germ cells (PGCs) . We have found that Steel factor and LIF synergistically promote the proliferation of PGCs. However, under these conditions, PGCs have a finite proliferative capacity that correlates with their cessation of division in vivo. In the presence of bFGF, LIF and membrane associated Steel factor but not soluble Steel factor, PGCs continue to grow over the finite proliferative capacity and give rise to colonies of cells resembling undiffer-entiated embryonic stem (ES) cells which can be subcultured. The PGC derived cell lines are indeed pluripotential and can give rise to chimeras when they are introduced into blastocysts. The long term culture of PGCs and the derivation of ES cells from them have implications for germ cell biology, the induction of teratocarcinoma and transgenic technology.