The vav proto-oncogene is universally and specifically expressed in hematopoietic cells. vav contains a unique array of motifs allowing the protein to function as a signal transducer and possibly as a transcription factor. Under certain in vitro culture conditions murine embryonic stem cells develop into colonies containing multiple hematopoietic lineages. In embryonic stem cell lines, constitutively expressing high levels of antisense vav transcripts through a stably integrated transgene, differentiation into hematopoietic cells is disrupted. This observation presents the first evidence that vav has a critical role in the development of hematopoietic cells from totipotent cells.