Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In the present study, we characterize NS cells in human BM. NS activity was found in a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T cells, B cells, and monocytes. The NS activity was significantly decreased by the depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells. Hematopoietic progenitor cells committed to the myeloid lineage were also enriched in the CD34+CD33+ cells, which significantly correlated to the NS activity. From these findings, it is strongly suggested that NS activity in human BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell contact was not necessary for the action, NS cells seemed to secrete soluble mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor were, however, not the candidates, based on experiments using neutralizing antibodies.