Previously, we reported evidence suggesting that, in addition to tyrosinase, glutathione-reductase plays an important role in the regulation and control of the biosynthetic activity of melanocytes. Further investigations were performed on a mammal presenting a well-defined genotype for coat pigmentation, the mutant mouse [subline C57 BL (6J)], namely the nonagouti black (a/a) mutant and the yellow (Ay/a) mutant showing, respectively, pure uniform eumelanin and phaeomelanin pigmentation. Analysis of thiol compounds and glutathione-related enzyme levels in mouse skin gave similar results to those found in tortoise-shell guinea pig skin. The observed differences in the glutathione and glutathione-related enzyme content between black and yellow (or red) skin provide evidence that the increase of glutathione-reductase activity in the environment of the melanocytes may stimulate the pigment cells to produce phaeomelanin instead of eumelanin pigment.