Interleukin (IL)-1α is one of the important cytokines involved in regulating immunological reactions in the mouse skin. However, it is not known whether IL-1α regulates the proliferation and differentiation of mouse epidermal melanocytes. In this study, to investigate the role of IL-1α in the regulation of the proliferation and differentiation of mouse epidermal melanocytes, IL-1α was supplemented to serum-free primary cultures of epidermal cell suspensions from the initiation of the primary culture (keratinocytes and melanoblasts-melanocytes) as well as to pure cultures of melanoblasts-melanocytes (keratinocyte-depleted cultures, after 14 days), and its effect was tested. IL-1α inhibited the proliferation of undifferentiated melanoblasts irrespective of the presence or absence of keratinocytes, whereas the cytokine inhibited the proliferation of differentiated melanocytes only in the presence of keratinocytes. Moreover, IL-1α induced the differentiation of melanocytes and, in addition, stimulated tyrosinase activity, melanin synthesis, and dendritogenesis of melanocytes irrespective of the presence or absence of keratinocytes. These results suggest that IL-1α is involved in inhibiting the proliferation of neonatal murine epidermal melanoblasts and in stimulating the differentiation, melanogenesis, and dendritogenesis of melanocytes. The results also suggest that IL-1α inhibits the proliferation of differentiated melanocytes in cooperation with keratinocyte-derived factors.