One of the most dramatic advances in biomedical research in the past 15 years has been the demonstration that human disorders can be studied in model organisms. This is a tribute to the investment of our country in basic biology. Genetic organisms such as yeast, Drosophila, C. elegans, and the mouse have led the way, but the organism par excellence for the study of thyroid hormone, one of the most important hormones for human health, is the amphibian, Xenopus laevis. Although vertebrates in all of the various phyla including humans require thyroid hormone (TH) to complete their life cycle, by far the most dramatic example is the role of TH in amphibian metamorphosis. TH is required absolutely for all of the remarkable changes that convert a tadpole into a frog. Many features of TH biology are identical in all vertebrates. However, the ease with which the model amphibian organism, X. laevis can be raised in the laboratory, the ability to manipulate TH levels, and the abundance of the material all make X. laevis the best model organism to study the action of TH. The mere addition of TH to the rearing water induces all of the events of metamorphosis. TH controls cell death, cell proliferation, and the remodeling of organs. Modem genetic methods are being applied to X. laevis with great success beginning with the new sperm mediated transgenesis technique of Kroll and Amaya. By expressing genes or mutant genes that interfere with metamorphosis in specific cell types the TH-controlled developmental program of a single cell type can be inhibited or activated selectively. The expression of detrimental gene products can be activated in cells at precise times in development utilizing controllable promoters. This wonderful old biological problem that previously could only be described by scientists is now yielding to modem molecular methods. ? ? ?