Four types of HIS mice can be generated with human FL-derived CD34+HSCs: HIS mice with no thymus, with a native mouse thymus, with a human thymus graft, or with both human and mouse thymi. To generate HIS mice with no thymus, NSG mice are thymectomized and 2 weeks later, sublethaly irradiated (100cGy) and injected i.v. with 1-2x105 human FL-derived CD34+HSCs. HIS mice with a native mouse thymus are generated similarly, except they were not thymectomized. Similar to the first group, HIS mice with a human thymus graft are thymectomized. Two weeks later, the mice are injected i.v. with HSCs and transplanted with autologous (to human HSCs) human fetal thymus fragments measuring about 1 mm³ under the kidney capsule. HIS mice with both human and mouse thymi are generated similar to the HIS mice with a human thymus, except they were not thymectomized.