Recombinant human interleukin 1 (IL-1) possesses potent inflammatory properties in both animal and human skin. However, IL-1-like material has been isolated from normal epidermal samples. In view of the uncertainty concerning the structure and biologic properties of human epidermal IL-1, heel stratum corneum, and chamber fluid samples from normal skin have been purified by successive reversed phase and anion exchange high-performance liquid chromatography (HPLC), and aliquots of each HPLC fraction tested for IL-1 activity in an EL-4 NOB-1 assay and for inflammatory activity by intradermal injection of autologous material. The results consistently indicated the presence of inflammatory quantities of IL-1 alpha-like material, which induced persistent erythema lasting at least 24 h, associated in 4-h biopsies with mixed dermal leukocyte infiltrates containing increased numbers of neutrophils, monocytes, and T helper cells. Biologically active quantities of IL-1 beta were not recovered following HPLC purification in most experiments. Analysis of heel stratum corneum extract also showed that the majority of the dilution-related IL-1 activity detected in the EL-4 NOB-1 bioassay was neutralized by IL-1 alpha but not IL-1 beta antiserum. These findings suggest that IL-1 alpha-like material is present in inflammatory amounts in normal human epidermis, and its release may represent a primary inflammatory mechanism in human skin. © 1990.