Greater than 90% of the endogenous thyroid hormone receptor proteins TR alpha and TR beta in tissues of Xenopus laevis comigrate with their respective in vitro synthesized counterparts, and these major components are not phosphorylated detectably. Maternally inherited TR alpha protein is stable through early embryogenesis during a time in which there is no detectable TR alpha mRNA synthesis. At stage 35 when TR alpha mRNA is first detectable, the inherited TR alpha protein is present at about 100 molecules/cell. TR alpha protein subsequently increases to levels of about 1500 and 6000 molecules/cell in tail and head regions, respectively, in stage 52 tadpoles. Even though TR alpha mRNA gradually increases during metamorphosis (from stage 52 to 62), TR alpha protein remains constant, suggesting strongly that post-transcriptional events control the ultimate levels of TR alpha protein. In contrast, there is no detectable TR beta protein (less than 100 molecules/cell) throughout embryogenesis until stage 52. Both TR beta mRNA and protein rise along with the increase in endogenous thyroid hormone, reaching a maximum at the climax of metamorphosis, when TR beta protein exceeds TR alpha protein in concentration. As with TR alpha protein, TR beta protein in tail is consistently about one-fourth that of TR beta protein in the head region. The number of TR alpha protein molecules in extracts of premetamorphic tadpoles and cultured cells grown in the absence of thyroid hormone fully accounts for all of the sites to which 125I-T3 bind. We interpret this to mean that TR alpha protein must be a necessary, if not sufficient, component in the pathway toward metamorphosis triggered by thyroid hormone and required for the phenomenon of competence in tissues and cells.