We have recently presented evidence that human plantar stratum corneum and psoriatic scales contain biologically active interleukin-1beta (IL-1beta) which has been activated in a process not involving interleukin-1beta-converting-enzyme. The aim of the present study was to compare this form of native IL-1beta with recombinant mature human IL-1beta as regards activity and the effects of inhibitors. In an assay based on the ability of IL-1 to induce the expression of E-selectin in cultured endothelial cells, the maximal activity of IL-1beta partially purified from plantar stratum corneum and recombinant IL-1beta was approximately the same. The specific activity was slightly higher for recombinant IL-1beta, although this difference was within one order of magnitude. An antibody to IL-1beta caused total inhibition of both forms of IL-1beta with no significant differences in the dose-response curves for the antibody. Immunochemical analyses and experiments with neutralising antibodies specific for IL-1alpha and tumor necrosis factor-alpha (TNF-alpha) verified that the observed activity in the partially purified preparation was due to IL-1beta, and not to IL-1alpha or TNF-alpha. There were no significant differences between the two forms of IL-1beta as regards the inhibitory effects of recombinant IL-1 receptor antagonist. Partially purified IL-1beta from plantar stratum corneum and from psoriatic scales were both highly active in the D10 proliferation assay. This activity could be totally inhibited with an IL-1beta specific antibody. This work thus confirms the presence of biologically active IL-1beta in plantar stratum corneum and psoriatic scales. Alternatively activated IL-1beta in the epidermis should be considered in future studies on skin biology and pathophysiology.