Interleukin 1β (IL-1β) is produced as an inactive 33 kD precursor, which becomes active after proteolytic processing to a 17.5 kD protein. A specific IL-1β-activating enzyme, interleukin 1β convertase (ICE), is present in e.g. monocytes. Human keratinocytes can express mRNA for IL-1β, in many conditions in an upregulated manner, but they do not express ICE. The role of keratinocyte IL-1β in normal and pathological conditions is therefore still unclear. In order to obtain more information in this area we have carried out analyses of hypertrophic plantar stratum corneum. This non-inflamed tissue has previously been shown to contain high amounts of IL-1-like activity.Extracts of human plantar stratum corneum were analyzed with specific ELISA-methods, with immunoblotting after denaturating one- and two-dimensional electrophoresis, and after iso-electric focusing of native proteins. Biological IL-1-activity was analyzed as the ability to induce ELAM-1 expression in cultured endothelial cells in the absence or presence of specific neutralizing antibodies.Similar amounts of biologically active IL-1α and IL-1β were found. The specific IL-1β activity was comparable to that of recombinant IL-1β. The IL-1β in plantar stratum corneum had a slightly higher molecular weight and a lower isoelectric point (close to 6.0 as compared to 6.9) than recombinant IL-1β, compatible with a cleavage of the IL-1β precursor at a site approximately 10 amino acid residues N-terminal of the ICE-site.We conclude: 1.) Human non-inflamed epidermis can produce biologically active IL-1β. 2.) The processing of the IL-1β precursor to biologically active IL-1β in the epidermis is catalyzed by an enzyme which differs from ICE.