The role of natural killer (NK) lymphocytes in the regulation of human hematopoiesis is controversial. NK-mediated inhibition of colony formation of hematopoietic progenitor cells has been irregularly reported for various cell lineages. In an effort to clarify such disparate findings, we studied the interaction of clearly defined NK and partially purified progenitor cell populations. Cell sorter purified CD16 positive blood NK cells and enriched autologous marrow progenitors were co-incubated at various lymphocyte to marrow cell ratios and then cultured in methylcellulose. There was no inhibition of myeloid, erythroid, or mixed colony formation. Similarly, activation of CD16 positive lymphocytes by interleukin-2 (IL-2) before co-incubation and co-culture did not result in inhibition of colony formation. Furthermore, in a newly designed assay system, we demonstrated that NK cells, which did not modulate colony-formation, remained capable of recognizing and killing rare K562 target cells seeded within the marrow cell population. Our results indicate that unstimulated and IL-2 activated isolated blood NK cells coexist with functioning autologous marrow progenitors in vitro.