Thyroid hormone receptors (TRs) are members of the fast growing superfamily of nuclear hormone receptors. They are dual function transcription factors. In the unliganded form, they repress basal transcription of their target genes. The presence of thyroid hormone leads to not only the relief of this repression but also a strong transcriptional activation above the basal level. Mechanistically, thyroid hormone receptors appear to function as heterodimers with 9-cis-retinoic acid receptors both in the absence and in the presence of thyroid hormone. Recent studies indicate that the heterodimers can interact with thyroid hormone response elements in chromatin independently of thyroid hormone and that the receptors have evolved to function efficiently in a chromatin environment, utilizing chromatin assembly to effectively repress transcription in the absence of thyroid hormone and overcoming the repression by chromatin by inducing chromatin disruption in the presence of the hormone. In addition, a number of TR-interacting proteins have been isolated. How these proteins participate in the regulation of transcription by TRs remains to be elucidated. Independent of the exact mechanisms of action, the developmental expression of thyroid hormone receptor genes during amphibian metamorphosis suggests that both the repression and activation functions of the receptors are important for proper control of the temporal and tissue-specific regulation of metamorphosis. Copyright 1996 S. Karger AG, Basel