- Biochemical studies show that in the process of mixed melanogenesis, cysteinyldopas are produced first which are next oxidized to give pheomelanin. After all of the cysteine is consumed, eumelanin is then deposited on the preformed pheomelanin. - In vitro and in vivo studies show that tyrosinase activity is the most important factor that regulates the switch of melanogenesis, with higher activities increasing melanogenesis, especially eumelanogenesis. - In culturted melanocytes, the tyrosine to cysteine ratio is critical in determining the eumelanin to pheomelanin ratio. - Our HPLC method to analyze eumelanin and pheomelanin has become a useful tool in the study of melanogenesis regulation. There are many problems to be solved before we fully understand the regulation of melanogenesis. Mutations in mouse models are ideal models for studying the genetic and molecular control of melanogenesis. Even in the mouse models, it is not known how cysteine is excluded from being incorporated into melanins in black and other eumelaninc mice, Conversely, it is not known how cysteine is continuously incorporated into pheomelanin in lethal yellow and recessive yellow mice.