In the present study, more than 200 generic drugs were screened to verify their applicability as a skin-lightening agent using mouse B16 melanoma cells. Of the numerous agents, danazol was found to inhibit melanogenesis in B16 cells in a dose-dependent manner with an IC(50) value of 9.3 μM. In addition, danazol reduced cellular tyrosinase activity in B16 cells but did not directly inhibit the murine tyrosinase activity in the cell-free system. Western blotting analysis confirmed that danazol downregulated the levels of tyrosinase protein in B16 cells, and reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed that danazol did not downregulate the levels of tyrosinase mRNA in the cells. These results indicate that danazol inhibits melanogenesis in B16 cells via reducing the tyrosinase activity by post-transcriptional regulation.