Human hematopoietic stem cells are contained within a population of marrow cells that expresses the CD34 antigen but not other antigens associated with commitment to specific lineages. Evidence that stem cells capable of maintaining long-term hematopoiesis are within this CD34+ lineage-negative (Lin-) population is reviewed, including in vivo studies in humans and nonhuman primates. In vitro studies of the CD34+ Lin-population have indicated that the blast-sized cells, which are presumably in cycle, proliferate and give rise to colony-forming cells in the presence of combinations of growth factors, including c-kit ligand and interleukin-3 (IL-3). Recent studies have examined the factors required for the growth of the quiescent subset of the CD34+ Lin-cells, identified as small to medium lymphocyte-sized cells that resist treatment with 4-hydroperoxycyclophosphamide, a known characteristic of the marrow-repopulating cell. These studies have shown that an interaction with marrow stromal cells is required, in addition to c-kit ligand and IL-3, to induce these cells to proliferate and form multiple colony-forming cells. These studies have further indicated that this effect of stroma is mediated by a soluble factor (s). This activity may represent a novel factor (s) and/or a novel combination of growth factors.