The in vivo effect of human recombinant IL-6 on hematopoietic stem cells (colony forming units in spleen, CFU-S) was investigated. Normal mice perfused with IL-6 for 7 days showed an increase in the serum level of IL-6 in a dose-dependent manner. This increase was accompanied by a dramatic enhancement (approximately 8-fold) in the number of spleen CFU-S 7 days after starting perfusion, although heat-treated IL-6 did not exhibit any activities. Enhanced CFU-S number returned to normal at 13 days after cessation of perfusion. These results suggest that IL-6 could be valuable for treating various forms of hematopoietic depletion.