Human immunodeficiency virus (HIV) disease is typified by declining CD4+ T lymphocyte counts in the peripheral circulation, a loss which may be secondary to accelerated destruction, to suppressed differentiation, and/or to sequestration of circulating cells into tissue spaces. As it is hard to distinguish between these possibilities in human subjects, the pathogenic mechanisms associated with HIV infection are unclear. In particular, little is known about the events that occur within infected lymphoid organs in which most CD4 T lymphocytes mature and function. To obtain a better description of HIV pathogenesis in vivo, we have implanted human haematolymphoid organs into the immunodeficient SCID mouse to create the SCID-hu mouse. We have previously shown that these organ systems promote long-term multilineage human haematopoiesis and are permissive for infection with HIV. Here we report that human thymopoiesis is suppressed by HIV infection, thereby precluding regeneration of the peripheral T-cell compartment.