The murine silver locus is one of the loci controlling hair color and its encoded product is thought to function in mammalian melanogenesis. Although we have recently shown that the silver locus protein is a melanosomal matrix protein and has none of the known eumelanogenic activities, its role in pheomelanogenesis is still unknown. In this study, we have compared the expression of the silver locus protein in pheomelanogenic and eumelanogenic hair bulb melanocytes along with those of tyrosinase-related proteins (TRPs). There was no detectable expression of the silver locus protein in hair bulbs of lethal yellow (A y /a) 10d old mice as well as TRP1 or TRP2. Similar results were observed in hair bulbs of 5 -7 d old agouti mice (A/A) when pheomelanin is produced predominantly. These results suggest that the silver locus protein might have a structural or unknown catalytic function which is eumelanogenesis-specific (e.g. a component of lamellar structures in eumelanogenic melanosomes).