Although stem cell transplantation is now a well established treatment modality for a wide variety of genetic, metabolic, immunologic and malignant disorders, there is still controversy concerning the optimal source(s) of stem cells. The present study examines the phenotypic characteristics of fetal bone marrow, cord blood and adult bone marrow stem cells and compares each of the following: 1) enumeration of CD34+ cells by FACS; 2) clonogenic activity measured by CFU-C assays, and 3) immunologic reactivity assessed by mixed lymphocyte reactivity (MLR) assay. A striking difference in the phenotypic composition of fetal and adult bone marrow as well as cord blood stem cells was observed (25.4% vs 3.1% vs 1.13%). The clonogenic/proliferative potential as measured by CFU-C assays was likewise significantly higher in fetal bone marrow when compared to adult or cord blood (202.5 vs 57.4 vs 73.5/105). Consistent with a finding of a lowered percentage of CD3+ T-lymphocytes in fetal bone marrow cells as compared to adult bone marrow and cord blood (1.5% vs 9.7% vs 8.1%), there was a significantly decreased proliferative responsiveness in MLR assays of fetal bone marrow and cord blood as compared to adult marrow (1x vs 3x vs 6x). These results show distinct differences as well as potential advantages of fetal over adult bone marrow stem cells or cord blood, which include a higher number of stem cells, a higher clonogenic/proliferative potential, and a lowered immunologic reactivity. These characteristics provide a basis for optimal conditions for engraftment of fetal cells without GVHD and support the use of fetal bone marrow for hemopoietic stem cell reconstitution and gene therapy. Moreover, these data indicate that each source of hemopoietic stem cells has different intrinsic properties closely correlated with ontogenic age that determines phenotypic characteristics, lineage commitments and level of reconstitution and engraftment which, collectively, may be vital in the design of novel therapeutic strategies.