We studied the inhibitory effects of 4-hydroxyphenyl alpha-glucopyranoside (alpha-arbutin) on melanogenesis in cultured human melanoma cells, HMV-II, and in a three-dimensional cultured human skin model. alpha-Arbutin showed no inhibitory effect on HMV-II cell growth at a concentration below 1.0 mM. Melanin synthesis in cells treated with alpha-arbutin at 0.5 mM decreased to 76% of that in non-treated cells. The cellular tyrosinase activity of HMV-II cells also significantly decreased, while the expression of its mRNA was not affected. Melanin synthesis in a human skin model was also evaluated by the macro- and microscopic observation of its pigmentation as well as by quantitative measurements of melanin. Treatment of the human skin model with 250 microg of alpha-arbutin did not inhibit cell viability, while melanin synthesis was reduced to 40% of that in the control. These results indicate that alpha-arbutin is an effective and safe ingredient for skin-lightening.