Rodents have been widely used for studies in transplantation immunology because of their short reproduction period and the relative ease of generating inbred mutant or transgenic strains. However, although many biological mechanisms are similar between rodents and humans, several features clearly distinguish the immune system in these species. Consequently, it is rarely possible to extrapolate observations from rodent models directly into clinical practice. In vitro studies with human cells are useful for elucidation of basic mechanisms, but in order to study complex biological phenomena, in vivo studies are indispensable. In later years, a number of interesting models have been described where immunodeficient mice have been reconstituted with human cells, so-called humanized mice, in order to study human immune responses in vivo. This has opened a new field of experimental immunology that has been applied to areas such as cancer, autoimmunity, allergy, infections, and transplantation biology. In this review, we shall concentrate on the use of severe combined immunodeficient mice reconstituted with human immune or stem cells for studies of human alloreaction in vivo.