Human fetal Merkel cells are now generally considered to be epidermal derivatives. Previous studies using antibodies against the simple epithelial cytokeratins (CKs), 8 and 18, have demonstrated the presence of these cells in the epidermis at as early as fetal week 10 to 12. Using antibodies against CK 20 whose expression within the skin is restricted to Merkel cells, we applied immunofluorescence and immunoperoxidase microscopy to analyze earlier embryonic and fetal human skin (wk 7 to 9). We were able to demonstrate the first Merkel cells at as early as fetal wk 8, i.e., at the same time as the epidermis starts to develop an intermediate, third layer, characterized by the expression of CKs 1, 10, and 11. Most of these early Merkel cells were localized above the basal layer. Their shape was round to oval, dendrites being infrequent and short. At fetal wk 9, Merkel cells were considerably more numerous. These results persuasively argue for a much earlier fetal development of Merkel cells within the epidermis than previously thought. A hypothesis concerning the differentiation of Merkel cells from embryonic basal keratinocytes is discussed.