AbstractThese studies were designed to explore further the interrelationships between various stem cell and other hematopoietic compartments of the mouse. Busulfan (BU) has been shown by others to have a profound effect on the transplantable pluripotent stem cells capable of forming colonies on spleens (CFU) of lethally irradiated recipients – more so than on cells of differentiated compartments. Another presumed assay of pluripotent stem cells consists of counting colonies on spleens of nontransplanted sublethally irradiated mice as a quantitation of endogenous colony‐forming units (E‐CFU). We examined and compared BU‐induced damage and recovery as measured by E‐CFU, CFU, CFU‐C, total cellularity of marrow, peroxidase‐positive cells per marrow, spleen weight, radioactive iron uptake into spleen and marrow, and hematocrit. E‐CFU were severely damaged by BU, but recovery was significantly more rapid than that measured for CFU. These results were compatible with other data suggesting that cycling stem cells are more likely to survive radiation and less likely to survive removal and transplantation. Thus, the actual number of pluripotent stem cells lies between the CFU and E‐CFU values. Damage to more mature granulocytic and erythrocytic compartments lagged behind damage to E‐CFU and CFU. Abortive rises in these more mature compartments were observed, which suggested limited but distinct self‐replication activity of “stem cells” more differentiated than the CFU, E‐CFU systems. Time of final recovery of the damaged hematopoietic system was compatible with a concept of recovery of pluripotent stem cell system(s) preceding recovery