The effect of captopril on melanin formation in B16 cells was investigated. In B16 intracellular model system, the effect of captopril on antityrosinase activity was found dose-dependent and correlated to its ability to suppress melanin formation. The copper chelation by captopril may in part be responsible for the inhibition of tyrosinase activity. Captopril also displayed a remarkable reducing ability and significantly inhibited ROS generation. Interestingly, captopril also significantly suppressed tyrosinase mRNA expression, as determined by reverse transcription-polymerase chain reaction (RT-PCR). Overall, the results showed that the protective effect of captopril makes it a potent inhibitor of melanin formation.