An animal model in which the human immune system can be reconstituted is necessary to study acquired immunity in vivo. We report here a novel model, the NOD/SCID/JAK3(null) mouse, for the human immune system's development. Newborn mice transplanted with human cord blood CD34(+) cells intrahepatically, developed human T and B cells, and myeloid and plasmacytoid dendritic cells. The T and B cells had a naïve to memory phenotype, and included plasma cells. The human acquired immune system can be reconstituted from CD34(+) cells in NOD/SCID/JAK3(null) mice. This model is a powerful tool for the study of human immunity.