To elucidate the mechanism for the specification of primordial germ cells (PGCs) in mice, we have developed and exploited the methods of single cell analysis. Based on these studies, we proposed a molecular program associated with this process, a key event of which is the repression of homeobox genes that are, without exception, upregulated in somatic neighbors. We have now identified Blimp1, a potent transcriptional repressor of a histone methyltransferase subfamily, as a key regulator of PGC specification. Indeed, the unexpected early onset of Blimp1 expression in a few cells at the most proximal-posterior epiblast cells marks the origin of the germ cell lineage. Disruption of Blimp1 function resulted in aberrant PGC-like cells with a deregulated intrinsic gene expression program at a very early stage, which demonstrates that Blimp1 is a critical determinant of the germ line in mice.