It appears that part of the confusion surrounding the lineage of NS cells could be due, in part, to the presence of more than one cell population in normal BM. Whether other cell populations exist in other organ compartments, or can be induced, is presently unknown. This is of particular interest in allogeneic BMT where various lymphocyte depletion techniques have been employed to reduce the incidence of AGVHD. When CCE is used for depletion, the NS lymphocyte component is entirely removed. Since the incidence of AGVHD is significantly reduced with CCE lymphocyte-depleted rat and human BM, it appears that this subpopulation need not be present to abrogate AGVHD. Quite surprisingly, preliminary studies in rats indicates that this lymphocyte subpopulation may actually induce acute syngeneic GVHD (Fischer et al., 1989). That a cell(s) in the clonogenic compartment has the ability to suppress or down-regulate a variety of immune responses is not altogether surprising. This cell is better thought of as an auto-regulatory cell which has the ability to control the cellular interactions in its immediate micro-environment. Indeed, R/O NSCA can be augmented by GM-CSF, IL-3, and CsA (NoGa et al., 1988a). In vitro, this cell differentiates into the mono-myeloid series using a variety of stimulatory agents and can acquire tumoricidal activity. The ability to express NSCA is lost however, being present only during a brief window of early maturation. Only IL-3 can sustain NSCA in culture.(ABSTRACT TRUNCATED AT 250 WORDS)