Melanotropins are synthesized as part of a large precursor molecule, proopiomelanocortin. This chapter reviews the evidence of the mechanisms of action of Melanophore-stimulating hormone (MSH) that has been obtained to support the following conclusions. These conclusions are: MSH binds to specific, high-affinity receptors on the cell surface; and formation of the hormone-receptor complex is followed by a stimulation of the adenylate cyclase system and a net increase in intracellular levels of Cyclic Adenosine Monophosphate (cAMP). The conclusions include: the hormone-receptor complex is internalized and apparently migrates to premelanosomes, the intracellular sites of melanin synthesis. They also include: the increased levels of cAMP result in increased tyrosinase activity and melanin deposition as well as changes in morphology and rates of proliferation; and these processes are mediated by cAMP-dependent protein kinases. In addition, improved techniques for synthesis and storage of mono I-ß-MSH is presented since this ligand has proven invaluable in studies on the structure and function of receptors for MSH.