The pigment effector cells of frog skin respond to many pharmacologic agents. The peptide hormones MSH and ACTH induce pigment granule dispersion, and melatonin causes melanin granule aggregation. The catecholamines produce both effects. Epinephrine, which stimulates both receptors and β-receptors in a variety of tissues, lightens skin previously darkened with MSH, and darkens light frog skin. Isoproterenol, a β-stimulator, produces only granule dispersion (darkening) and phenylephrine, an α-adrenergic agonist, causes only granule aggregation (lightening). The effects of catecholamines, MSH and caffeine, on the pigment cells of frog skin are best explained through the mediation of adenyl cyclase and cyclic-AMP.