Hyperpigmentation disorders such as freckles and senile lentigines in the skin are associated with abnormal accumulation of melanin pigments. In this study, two lignan constituents were isolated from Saururus chinensis Baill (Saururaceae) as inhibitors of cellular melanin production by bioassay-guided fractionations. The active constituents were manassantin A and B that dose-dependently inhibited melanin production in alpha-melanocyte stimulating hormone (alpha-MSH)-activated melanoma B16 cells with IC(50) values of 13 nm and 8 nm, respectively. Arbutin as a positive control exhibited an IC(50) value of 96 microm on alpha-MSH-induced melanin production. Further, manassantin A inhibited forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production with IC(50) values of 14 nm or 12 nm, respectively. Manassantin A decreased cellular amounts of IBMX-inducible tyrosinase protein but could not affect the catalytic activity of cell-free tyrosinase, a key enzyme in the biosynthetic pathway of melanin pigments. Finally, this study could provide a pharmacological potential of S. chinensis in hyperpigmentation disorders.