Steel factor (S1F), also known as stem cell factor, is a potent growth stimulator of hemopoietic progenitor cells. In the context of transplantation of hemopoietic cells to irradiated allogeneic hosts, natural killer (NK) cells exert restrictive control on hemopoietic cell proliferation, and are regularly found in elevated concentration in areas of intense hemopoiesis. The present study was designed to examine the effects with time of S1F in vivo on the numbers of NK cells, identified by the presence of the NK 1.1 surface molecule, in the spleen and bone marrow. Throughout the first 3 days of S1F exposure, NK cell numbers, in spite of rapid (1 day) and significant increases in the other hemopoietic cell lineages, did not change in either the spleen or the bone marrow. However, NK cells were increased 2-fold in both organs by 7 days of S1F exposure. At this time, immature granuloid and erythroid cells and the large lymphoid cells in the spleen had more than doubled their respective control numbers and in the bone marrow, immature granuloid cells increased by 47% of control levels. The presence of a late, but not early, influence of S1F on NK cells of the spleen and bone marrow suggests an indirect effect of S1F on this lineage, occurring only when S1F-stimulated hemopoiesis becomes sufficiently intense, providing, thus, an abundance of NK cell targets.