We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (FcϵRI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a^bright/CD1b^neg/FcϵRI^dim/CD23^neg/CD32^dim/HLA-DR^bright/CD36^negpopulation was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a^bright/CD1b^neg /FcϵRI^bright /CD23^neg/CD32^dim/HLA-DR^bright/CD36^dim, while the second population was CD 1a^dim/CD1b^dim/FcϵRI^bright/CD23^dim/CD32^dim/HLA-DR^bright/CD36^bright. The highest FcϵRI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, FcεRI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of FcεRI in atopic eczema skin.