Embryonic stem (ES) cells have the pluripotency to differentiate into any cell types in vitro, including cells of the germ lineage. However, the mechanisms that lead ES cells to differentiate into germ cells in vitro remain unknown and the efficiency of reported in vitro systems is poor. We have attempted to find a more defined and efficient way to derivate sperm and oocytes from mouse ES cells in vitro by manipulating genes such as Daz and Dazl. The gene Daz (deleted in azoospermia), which is essential for sperm development in humans, is expressed in ES cells, as well as in male and female germ cells. In mice, its homolog, Dazl, is turned off once mouse ES cells undergo somatic differentiation, but its expression is maintained in germ cells. Dazl deficiency can lead to embryonic arrest of germ cell development in mice. Here, we report that Dazl as a transgene can promote gametogenesis of mouse ES cells. Overexpression of Dazl can induce both tailed-sperm and oocytes from the same mouse ES cells in vitro. This finding may provide a novel in vitro approach to generate gametes from embryonic stem cells and to study gametogenesis of embryonic stem cells.