The mechanism which produces marrow failure in idiopathic aplastic anemia is still unknown. Recent investigations have suggested the crucial role of NK cells in the regulation of normal hematopoiesis. In this study, the cytotoxic activity of mononuclear cells from human bone marrow and peripheral blood was examined against three NK-sensitive target cell lines in 15 patients with aplastic anemia as well as 21 normal subjects. Marrow mononuclear cells from aplastic anemia demonstrated a high cytotoxicity comparable to peripheral blood NK cells to these target cells. Neither large granular lymphocytes nor the cells expressing known NK cell surface phenotypes increased in aplastic marrow cell elements. The aplastic marrow cells showed strong killing activity rather than binding at single cell assay. They consisted of non-adherent and adherent cell population in plastic adherence and were unresponsive to IFN treatment. The existence of cytotoxic cells with high NK-like activity may be responsible for the mechanism of marrow failure in aplastic anemia.