The transcription factor Oct-4 is expressed in totipotent embryonic cells and germ cells. As totipotent cells differentiate to form somatic and/or extraembryonic tissues, the Oct-4 gene is downregulated. Primordial germ cells are the only cells in which Oct-4 expression is maintained after postgastrulation. Recent in vivo ablation of the Oct-4 function has shown that the absence of this transcription factor causes early embryonic lethality due to trophectodermal differentiation of cells which normally would give rise to the inner cell mass of the blastocyst. This result strongly suggests that Oct-4 is necessary for the maintenance of the totipotent phenotype of embryonic cells and that this factor likely plays a role as a determinant of the totipotency of germ cells by preventing their differentiation to a somatic cell phenotype during gastrulation. The involvement of Oct-4 in the biology of totipotent and germ cells is here discussed in view of new understanding about Oct-4 function. Mol. Reprod. Dev. 55:452–457, 2000. © 2000 Wiley-Liss, Inc.