Abstract: A chimeric, non-human, genetically-immunocompetent mammal is disclosed. The hematopoietic system of the mammal has human passaged bone marrow stromal cells and human hematopoietic stem cells obtained from a CD34.sup.+ -enriched bone marrow fraction, and also contains transplanted syngeneic non-lymphoid spleen colony cells. The mammal may be a mouse, a rat, a rabbit, a cat, a dog, a pig, a sheep or a non-human primate. The mammal can be produced by providing a non-human, genetically-immunocompetent mammal in which its immunologic genotype comports with the norm for the species of the mammal, exposing the mammal to a level of x- or gamma-radiation that is sufficient to destroy substantially all bone marrow in the mammal to render the mammal phenotypically immunodeficient, then transplanting into the mammal syngeneic non-lymphoid spleen colony cells and human passaged bone marrow stromal cells, and transplanting into the mammal human hematopoietic stem cells obtained from a CD34.sup.