Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a+ and CD1a- monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIa-positive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a+ and CD1a-cells showed intracytoplasmic granules that were different from LC Birbeck granules. These phenotypical and ultrastructural features are comparable to those of CD14-derived DC obtained from cord blood precursors [C. Caux et al. J. Exp. Med. 184, 695-706]. These results show a close relationship between these two in vitro models, which are both related to dermal DC.