Summary: Cre transgenic mice can be used to delete gene sequences flanked by loxP sites in specific somatic tissues. We have generated vavCre transgenic mice, which can be used to inactivate genes specifically in adult hematopoietic and endothelial cells. In these animals, a Cre transgene is expressed under control of murine vav gene regulatory elements. To assess their usefulness, vavCre transgenic mice were bred with R26R mice, which express a lacZ reporter gene only in cells where Cre‐mediated recombination has occurred. VavCre/R26R double‐heterozygous offspring were analyzed by β‐galactosidase histochemistry and flow cytometry. VavCre‐mediated recombination occurred in most hematopoietic cells of all hematopoietic organs, including the hematopoietic progenitor‐rich bone marrow. Recombination also occurred in most endothelial and germ cells, but only rarely in other cell types. The recombination in both hematopoietic and endothelial lineages may partly reflect their putative shared ontogeny and provides a unique tool for simultaneous pan‐hematopoietic and endothelial mutagenesis. genesis 34:251–256, 2002. © 2002 Wiley‐Liss, Inc.