The present study was designed to address whether melanoston which was extracted from yeast was able to induce depigmentation of the skin in guinea pigs. The activity of tyrosinase which participates in the synthesis of melanin pigment residing in melanocytes of guinea pig's epidermis was assessed using immunohistochemical staining methods with anti-tyrosinase antibody. To determine whether melanoston affects the processes of melanin synthesis in melanosome of melanocytes, melanoston-applied skin was examined by electron microscopy following immunogold tagging methods. We obtained results as follows: 1. The activity of tyrosinase was the lowest 3 weeks after application of 0.1 and 0.01% melanoston on the skin of guinea pigs. 2. The frequency of immunogold particles distributed in melanocytes and keratinocytes was lowest 3-4 weeks after application of 0.5 and 0.1% melanoston. Thus, these results suggest that melanoston has a potential to inhibit synthesis and distribution of melanin in the epidermis.