INTRODUCTIONThe Mexican axolotl (Ambystoma mexicanum) follows a very different pattern of development from other closely related tiger salamanders. Whereas many tiger salamanders undergo an obligatory metamorphosis, axolotls rarely if ever transform in the lab. As a consequence, axolotls retain larval features into adulthood and therefore require aquatic husbandry procedures throughout life. However, it is possible to induce metamorphosis in axolotls by simply adding thyroid hormone to the rearing water. If thyroid hormone is provided at an appropriate concentration and at a time during development that related tiger salamanders normally transform, healthy and robust terrestrial axolotls can be generated. The procedure is useful for studying molecular mechanisms of tissue-specific developmental programs that depend upon thyroid hormone. Also, because thyroid hormone brings about the maturation of tissues, the axolotl model can be used to study the molecular correlates of aging. Finally, the axolotl model can be used to study ecotoxicological factors that disrupt thyroid hormone signaling and tissue remodeling. The ability to precisely activate metamorphosis in the axolotl provides an advantage over anuran models that are always developing toward a metamorphic outcome. The protocol described here induces metamorphosis in axolotls using the less active form of thyroid hormone called T4 (tetraiodothyronine).