The purpose of this study was to investigate effects of myriocin, an inhibitor of serine palmitoyltransferase, on melanogenesis. It was found that myriocin increased melanin synthesis in a concentration-dependent manner. Moreover, myriocin up-regulated microphthalmia-associated transcription factor (MITF) and tyrosinase expression via phosphorylation of CREB, but it did not directly activate tyrosinase, a rate-limiting melanogenic enzyme. Furthermore, we demonstrated increased melanin synthesis with myriocin on a pigmented skin equivalent model established using Cervi cornus Colla (deer antler glue). One and 5 microM of myriocin darkened the color of the skin equivalent. These results suggest that myriocin may have potential effects for the treatment of hypopigmentary skin diseases like vitiligo or for sunless tanning.