Interleukin 6 (IL 6) was detected in the culture supernatants of human epidermal keratinocytes and its production was enhanced by stimulation with cytokines. Production of IL 6 in keratinocytes was demonstrated directly by immunohistochemical staining of cultured cells with anti-IL 6 antibody. Keratinocyte-growth was increased by stimulation with recombinant IL 6 (as measured by either [3H] thymidine uptake or direct cell count). Moreover, expression of IL 6 receptor was demonstrated on monolayered cells, and the deeper cells of stratified keratinocytes in culture by immunohistochemistry. On the other hand, differentiated cells in the upper layers did not express IL 6 receptor on their surfaces, suggesting that the expression of IL 6 receptors may be confined to the proliferative cells. Thus, IL 6, which is produced by epidermal keratinocytes, may be involved in the regulation of normal keratinocyte growth.