AbstractThe mouse melanoma cell line B16/C3 offers an excellent in vitro model for studying melanocyte differentiation. Melanogenesis can be induced by serum, a hormone‐supplemented serum‐free medium, melanocyte stimulating hormone, and dibutyryl cAMP. The tumor promoter, 12‐O‐tetradecanoyl‐phorbol‐13‐acetate, 5‐bromodeoxyuridine, and acidic pH inhibit this process. Using two‐dimensional polyacrylamide gel electrophoresis, we have identified four cellular proteins whose production is modulated during melanogenesis, a process which includes concomitant increases in levels of ty‐rosinase, the rate limiting enzyme for melanin biosynthesis, melanization, and ultimately, cell death. The production of these proteins are coordinately expressed or inhibited in response to the diverse inducers and inhibitors of melanogenesis. We conclude from these studies that these specific proteins are intimately involved in the differentiation of B1