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Current research guidelines for ectothermic tetrapod vertebrates prohibit the use of cold as an adjunct to gaseous anesthesia, and they prohibit freezing as a means of euthanasia of these same animals. Here, we argue that those guidelines merit re-evaluation. Under natural conditions, numerous amphibians and reptiles experience large variations of body temperature, and life at low temperatures is natural. In tropical species less tolerant of cold, nociception is likely to be extinguished at low temperatures because of the anesthetizing actions of cold on membranes and cold block of nerve conduction. Physical principles and physiological data suggest that smaller ectothermic vertebrates do not experience pain attributable to ice crystals that form during freezing. Therefore, whole-body cooling, followed by freezing, should be a humane form of euthanasia for numerous smaller ectothermic species. In addition, we believe that cooling offers a humane and useful means of supplementing currently acceptable methods of anesthesia.