Although diseases of blood cells constitute a relatively small proportion of clinical disorders, many valuable studies of gene transfer have relied on hematopoietic stem cells or their progeny. What features of these cells explain their appeal in gene therapy? Perhaps most important is their hierarchical pattern of development (Figure 1). Fewer than 1 in 100,000 bone marrow cells are pluripotent, self-renewing hematopoietic stem cells, but these rare cells yield progeny that multiply by many hundredfold and, in the process, follow a particular blood-cell lineage (monocytic, lymphocytic, granulocytic, megakaryocytic, or erythrocytic). These committed progenitors then multiply by a hundredfold or more . . .