Mice carrying inactivated Rh and Rhag genes were generated by insertional targeting. KO animals exhibited normal growth, development and fertility and both types were indistinguishable at a gross phenotypic level from their wild type littermates. Preliminary analysis revealed that red cells from Rh-/- mice lack Rh protein and have a moderate decrease of Rhag protein, whereas those from Rhag-/- mice have a total absence of Rhag and Rh proteins. Studies are in progress to delineate the antigenic, biochemical and functional abnormalities of red cells from these animals as well as the impact on hematological parameters and erythropoiesis.