Epidermal Langerhans cells (LC) are related to certain cells of the monocyte-macrophage lineage and to other dendritic cells. While epidermal LC and macrophages bear receptors for the Fc portion of IgG, other dendritic cells do not. However, unlike human dendritic cells from peripheral blood, LC bear the antigen against which the OKT6 antibody is directed. Within the skin this antibody binds only to LC or indeterminate cells. Functionally LC and dendritic cells can present antigen to sensitized T cells and are capable of stimulating allogenic T cells. Since lymphokines are thought to play an important role in T-cell activation and since LC are potent stimulators of antigen-specific T-cell proliferation, we investigated whether LC could produce interleukin-1 (IL-1). Our initial studies revealed that whole epidermal cell suspensions comprised of LC, keratinocytes, and melanocytes produce a factor that is similar to macrophage-derived IL-1. We termed this factor epidermal cell-derived thymocyte-activating factor ( ETAF ). Using a panning technique we obtained a highly enriched (up to 97%) population of LC which constitutively produced significant IL-1-like activity. Using an antibody against the monocyte-derived leukocytic pyrogen (LP) which has been shown to inhibit IL-1 activity, we were able to inhibit IL-1 activity from LC-enriched cultures. The results of this study indicate that within the epidermis there are at least two cell populations, keratinocytes and LC, that can constitutively secrete potentially important soluble immunostimulatory factors.