The zinc-finger transcription factor Ovol2 (Movo, Movo2) is a mouse homologue of Drosophila ovo, which is essential for the survival and differentiation of female germ line cells. To elucidate OVOL2 function in mammals, we generated Ovol2-deficient mice by gene targeting. The Ovol2 mutants died at embryonic days 9.5-10.5 (E9.5-E10.5), as a result of defects in extraembryonic and embryonic vascularization, and in heart formation. Although the Ovol2 expression was weak, severe defects were detected in extraembryonic and embryonic vascularization, and in heart formation at E8.5-E9.5. In Ovol2(-/-) placentas, allantoic blood vessel expansion and development of the labyrinthine layer were impaired at E10.5. In an endothelial cell line, siRNAs for Ovol2 reduced the expression of Ovol2 and inhibited the capillary-like network formation on Matrigel in vitro. These results demonstrate that Ovol2 may play a critical role in vascular angiogenesis during early embryogenesis.