Since the discovery of the CD34 stem/progenitor cell antigen, considerable progress has been made in further purifying human lymphohematopoietic stem cells (HSC). These studies have identified a number of antigens which can be targeted to subfractionate the CD34+ cell population. In particular, several lines of evidence suggest that the rare CD38(-)subpopulation of CD34+ cells may be enriched in HSC. This review briefly summarizes relevant knowledge concerning the CD38 molecule and the results of in vitro and in vivo studies of CD34+38(-)cells. Possible clinical uses for purified CD34+38(-)cells are outlined.