SYNOPSIS. The present paper is concerned mainly with the melanin-dispersing effect of melanocyte-stimulating hormones (MSH's) on the skin melanophores of amphibians. In addition, some of the more recent evidence for the unihumoral theory of the control of color change is reviewed. The mechanism of dispersion of melanin is still unknown, but evidence is accumulating that the action of MSH may be mediated by an increase in the melanophoric content of adenosine 3', 5'-monophosphate (cyclic AMP). For example, cyclic AMP has a specific, reversible melanin-dispersing effect on the melanophores of the isolated skin of R. pipiens and Xenopus laevis. It also has a reversible “melanophore—expanding” effect on the tissue—cultured embryonic melanophores of the spotted salamander, Ambystoma maculatum. The effect of cyclic AMP on melanophores of R. pipiens does not require sodium but is inhibited by hypertonicity. Finally, new evidence is presented that confirms that the melanin-dispersing effect of catecholamines on melanophores of X. laevis is mediated by beta adrenergic receptors,because it is blocked by the highly specific β—blocking agent, propranolol. On the other hand, the melanin-aggregating effect of catecholamines on amphibian melanophores appears to be mediated by alpha adrenergic receptors. There is even a possibility that the effects of catecholamines are also mediated through a control of cyclic AMP levels in melanophores, with beta adrenergic stimulation producing an increase in cyclic AMP levels, followed by dispersion of melanin, and alpha adrenergic stimulation producing a decrease in cyclic AMP levels, followed by aggregation of melanin.