The regulation in the skin of interleukin-15 (IL-15), a potent modulator of T-cell-mediated immune responses, is not fully understood. We investigated the levels of IL-15 and its mRNA produced by epidermal and cultured keratinocytes and found that normal keratinocytes did not constitutively express IL-15 in the epidermis, but in culture began to produce the cytokine. Some epidermal keratinocytes expressed IL-15 in inflammatory conditions associated with infiltration of neutrophils and eosinophils. IL-15 was detected only in the cell lysates, not in the supernatants of cultured keratinocytes. Dexamethasone (10(-5)-10(-6) M) markedly inhibited IL-15 mRNA expression by normal and transformed keratinocytes in a range of pharmacological concentrations. IFN-gamma (200 and 400 U/ml) slightly increased the IL-15 message level in a squamous cell carcinoma cell line, HSC-5, in a dose-dependent fashion, whereas no significant change was observed in cultured normal human keratinocytes. Our data indicate that IL-15 is not a constitutive cytokine in epidermal keratinocytes but is inducible.