The peptide hormone α-melanotropin (α-MSH) is well known to stimulate pigment dispersion in dermal melanophores of lower vertebrates and pigment formation in epidermal melanocytes and melanoma cells. The effects of the second messenger cyclic adenosine monophosphateare mediated by cyclic adenosine monophosphate-dependent protein kinases through the phosphorylation of a wide variety of substrate proteins. The other type of calcium-dependent protein kinase is protein kinase C. In melanophores, α-MSH-receptor activation is thought to stimulate membrane-bound adenylate cyclase activity, thus increasing intracellular levels of cyclic adenosine monophosphate. Extracellular calcium is well known to be required for the mechanism of action of α-MSH on melanophores of different species, including the melanophores in the ventral tailfin of X. laevis tadpoles. MSH-induced changes in protein phosphorylation appear to be rapid and reversible. The time-courses of these effects on phosphorylation suggest that phosphorylation is involved in the initiation of cellular response to α-MSH, such as pigment dispersion and synthesis.