G-CSF primed CD34 cells cultured for 2-3 weeks in IL-2 and stem cell factor generate CD56 high cells with phenotypic and morphologic features of NK cells, and a novel adherent CD56 low CD16À population expressing myeloid markers (CD33 and HLA-DR). We hypothesized that similar cells might also occur in peripheral blood. In 13/13 normal individuals, we found a circulating population of CD56 low , CD33 þ , FccRI þ , FccRII þ , HLA-DR þ , CD11b high , CD14 þ monocytes closely resembling the cultured CD56 low CD33 þ cells. They may represent a normal counterpart of the CD56 þ CD33 þ hybrid myeloid/natural killer cell leukemia. Their mean frequency was 1.371% (standard deviation), range 0.16-3.5%, of total mononuclear cells. CD56 low CD33 þ cells, primed with cytomegalovirus antigen, induced autologous T-lymphocyte proliferation comparably to CD56À, CD14 þ peripheral blood monocytes (PBM). Conversely, CD56 low cells induced greater T-cell proliferation than CD56À PBM when lymphocyte responders were HLA mismatched. Unstimulated CD56 low CD33 þ cells showed a low antiproliferative effect on K562, which was increased upon LPS stimulation. The pattern of cytokine production by CD56 low CD33 þ cells and PBM largely overlapped; however, they produced detectable levels of IL-6 and IL-1b. These results define a minor monocyte population with distinct phenotypic and functional features.