Summary: Whether a freshly isolated immune cell can be equipped with both natural killing and antigen-presenting cell (APC) function has recently become controversial in mice. We sought to probe the existence of a candidate human cell with these properties by searching for cells in healthy subjects that co-express APC surface molecules and NK cell receptors. We have found that CD3−CD14−CD19− mononuclear cells of human blood, spleen, liver, and lymph nodes contain two distinct populations of cells that co-express HLA-DR (DR) and CD56. Circulating CD56+ cells expressing high levels of DR were phenotypically and functionally similar to conventional CD56−dendritic cells (DC). Furthermore, we demonstrate here that a separate cohort of CD56+ cells that express low levels of DR are NK cells that possess dual function as potent killers endowed with weak APC function. [Copyright &y& Elsevier]