McCord and Allen (1917) found that extracts of mammalian pineal glands contain a potent contracting agent of larval amphibian melanophores. Lerner and his co-workers determined the chemical structure of this principle and named it melatonin. This agent contracts dermal melanophores at a concentration as low as 10−10 g/ml. Both intact and eyeless larval amphibians blanch when placed in the dark, and the melanophore contraction which causes this lightening response is abolished by pinealectomy. The amphibian pineal contains photoreceptive elements similar to those found in the vertebrate lateral eyes, and these elements are inhibited by light but are stimulated in its absence. There is evidence for the presence of both HIOMT and melatonin the amphibian pineal. It has been proposed that the body-blanching response results from a direct stimulation of the pineal under conditions of darkness leading to a release of melatonin into the general circulation which is then responsible for a direct contracting effect on dermal melanophores. The cytophysiological effects of melatonin mimic those that take place in the body-blanching response. Since no other hormone or pharmacological agent duplicates this response, this is strong evidence that melatonin is a hormone that normally regulates body blanching. Other evidence for the support of this hypothesis is presented. Cytological features of both normal and melatonin-induced lightening indicate that the effects of melatonin are at the effector cell level rather than at either the hypothalamus or the pituitary. An inhibition of MSH-release by melatonin is not involved. Melatonin plays a normal role in young larvae to regulate the lightening response that takes place in darkness (the primary chromatic response). Neither melatonin nor the pineal play a role in the later (secondary stage) adaptive background responses of amphibians. As McCord and Allen first noted, the pineal may contain other substances which may have other physiological roles in amphibians as well as other vertebrates. These have been little studied.