Dendritic cells (DC) generated from peripheral blood monocytes have been used with promising results as a new approach for the immunotherapy of cancer. However, at least four different subpopulations of peripheral blood monocytes have been recognized and their contribution to the generation of functional DC is not known. Recently, the monoclonal antibody M‐DC8 has been shown to react with 0.2 – 1 % of blood leukocytes. We have identified M‐DC8⁺ cells as monocytes which represent about 40 % of CD14^lowCD16⁺ monocytes. Similar to M‐DC8^– monocytes, they develop in the presence of GM‐CSF and IL‐4 into a very homogenous population of cells with DC phenotype and function. M‐DC8⁺ DC show on average a twofold higher expression of HLA class I and class II molecules than M‐DC8^– DC. These DC produce IL‐12p75 both in response to LPS and to CD40 ligation. M‐DC8⁺ DC induced a strong Th1 immune response and were two to four old more potent than M‐DC8^– DC for the priming of cord blood T cells. M‐DC8⁺ monocytes can be used as a source of very potent dendritic cells with the potential to significantly improve the efficacy of DC‐based immunotherapies.