Inbred mice with specific genetic defects have greatly facilitated the analysis of complex biological events. Several humanized mouse models using the C.B.-17 scid/scid mouse (referred to as the SCID mouse) have been created from two transplantation protocols, and these mice have been utilized for the investigation of human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) pathogenesis and the evaluation of antiviral compounds. To generate a more prominent small animal model for human retrovirus infection, especially for examination of the pathological process and the immune reaction, a novel immunodeficient mouse strain derived from the NOD SCID mouse was created by backcrossing with a common gamma chain (gamma(c))-knockout mouse. The NOD-SCID gamma(c)null (NOG) mouse has neither functional T and B cells nor NK cells and has been used as a recipient in humanized mouse models for transplantation of human immune cells particularly including hematopoietic stem cells (HSC). From recent advances in development of humanized mice, we are now able to provide a new version of the animal model for human retrovirus infection and human immunity.