The mRNA level of the two Xenopus laevis thyroid hormone receptor beta (TR beta) genes is up-regulated in tadpoles and cultured cells by the addition of thyroid hormone (TH). Up-regulation of transcripts of the 5' most exon is detectable 2-3 h before that of full-length TR beta mRNA, strongly suggesting that up-regulation is under transcriptional control. The TH-induced up-regulation in cultured cells is inhibited by cycloheximide when measured either by a transcription initiation assay that measures transcripts of the 5' most exon or by synthesis of full-length TR beta mRNA. From this we conclude that in cultured cells protein synthesis is required for up-regulation of TR beta mRNA. The up-regulation of TR beta mRNA by TH in tadpoles is only partially inhibited by protein synthesis inhibitors. A survey of "thyroid response" genes in the literature reveals that the reported change in gene expression is, in most cases, sensitive to protein synthesis inhibition. This is true of genes with demonstrable thyroid hormone response elements. If an unknown protein must be synthesized to effect up-regulation of a thyroid hormone response gene, it calls into question assays that only take into account the binary reaction between thyroid hormone receptor and a putative thyroid hormone response element.