Human hematopoietic progenitor cells (HPCs) from mobilized peripheral blood mononuclear cells (PBMCs), adult bone marrow (ABM), and fetal bone marrow (FBM) were evaluated for their ability to produce multilineage human hematopoietic engraftment in vivo. Sublethally irradiated BNX (beige/nude/xid) mice were injected with either unfractionated cells or CD34+ cells purified from these sources. The presence of human cells in the mouse PB, BM, and spleen was evaluated by flow cytometry at either 6 to 8 weeks or 6 months postinjection. Recipients with > or = 1% human cells in any of these tissues were considered chimeric. Of 26 mice injected with FBM, 4 showed up to 73% human cells in the BM or spleen at 6 months. The phenotypes of these cells included CD13/33+ myelomonocytic cells (38%), CD19+ B cells (67%), and CD34+ progenitor cells (28%). In contrast, ABM gave rise to a mean of 5% human cells in the PB in 2 of 42 (4%) recipients at 6 to 8 weeks. These circulating human cells were predominantly CD3+, whereas CD13/33+ and CD34+ cells were detected in the BM for up to 6 months. A total of 18% of mice injected with PBMCs showed a mean of 36% human cells in the PB. Both the BM and spleens of PBMC-injected mice contained CD3+ cells in a proportion similar to that observed in the PB. These CD3+ cells were phenotypically mature CD4+,CD8- or CD4-,CD8+ T cells and coexpressed a variety of Vbeta T-cell receptor (TCR) genes. The percentage of CD3+ cells in the circulation of chimeric recipients injected with either FBM, ABM, or PBMCs correlated well with the input CD3+ cell dose for each of these HPC sources (r = .99). The high levels of engraftment of CD3+ cells in recipients of PBMCs and the long-term multilineage engraftment of FBM recipients have important implications for developing strategies to study the regulation of these human cells in vivo.