Human embryonic and fetal epidermis was examined and labeling indices (LIs) for basal, intermediate, and periderm cells were determined. The LI for fetal basal cells was 8-11% and the LI for fetal intermediate cells was 7.5-9%. The total fetal epidermal LI was 16-20%, which equaled the basal LI for embryonic epidermis. After 21 days in organ culture, only basal cells in the fetal epidermis labeled with tritiated thymidine, while both basal and intermediate cells in the embryonic epidermis labeled and the total LI for fetal and embryonic epidermal cells was the same as the adult epidermal LI (7%). The LI for periderm decreased with increasing estimated gestational age (EGA) from 9.5% at 49 days EGA to 0.4% at 85 days EGA. A subpopulation of epithelial cells that retained tritiated thymidine label and that have some of the attributes associated with stem cells has been previously demonstrated in rodents. In order to examine human embryonic and fetal epidermis for the presence of such cells, epidermis from various gestational ages were labeled and grown in organ culture for 21 days. The mean percent label-retaining cells (LRCs) for embryonic and fetal epidermis was determined. Approximately 4% of the embryonic and 2% of the fetal epidermal cells retained label for 21 days in organ culture. Embryonic LRCs were found in the basal and suprabasal layers, but fetal LRCs were found only in the basal layer. The presence of LRCs in human embryonic and fetal epidermis suggests that epithelial cell proliferation in these tissues may be regulated via a stem cell pattern of proliferation.