Natural killer (NK) and T subsets were analyzed with appropriate dual labeling by flow cytometry in peripheral blood (PB) (66 cases) and bone marrow (BM) (55 cases) from patients with de novo AML in order to determine: (a) their distribution at diagnosis, (b) the correlation between PB and BM in NK subpopulations, (c) their relationship with the clinical and hematological disease characteristics, and (d) the changes occurring upon achieving complete remission (CR). NK cells defined by the expression of CD56 in the absence of CD3 were significantly increased at diagnosis and their levels in PB correlated with those of BM. By contrast, NK subsets defined by CD16 expression (CD16+ CD2+ and CD16+ CD2- NK-cell subsets) as well as T lymphocytes with NK activity (CD56+ CD3+), although increased in PB, displayed normal levels in BM. An additional observation of interest was the expansion of an immature NK population lacking CD16 Ag expression (CD56+ CD16-). AML cases were divided into two groups according to the absolute number of NK cells in PB; patients with the highest levels showed an increased proportion of blast cells in PB (p = 0.01), monocytic subtypes (p = 0.03), and expression of CD11b, CD14, and CD4 antigens (p = 0.05). Infections at diagnosis were not related to the level of NK cells. In 19 patients who achieved complete remission the number of CD56+ CD3- cells tended to be reduced to within the normal range. Other T-cell populations, including the CD4 naive and memory cells, were also explored, their distribution being normal in the PB of AML patients. By contrast, the cytotoxic subset CD8+/CD57+ was significantly increased (p < 0.001). These data point to the existence of marked alterations of NK cells in AML patients, possibly reflecting a host-tumor immunological interaction.