Although the role of the three functional thyroid hormone receptor isoforms (TR beta 1, TR beta 2, and TR alpha 1) remains unclear, studies by Hodin and Lazar et al. have suggested that restriction of TR beta 2 messenger RNA (mRNA) to rat pituitary could reflect a specific regulatory role in the pituitary. Supporting their hypothesis was a significant fall in pituitary TR beta 2 mRNA after T3 administration. These observations prompted us to assess the effect of thyroidal state on the level of TR beta 2 protein, as inferred by immunoprecipitation of TR beta 2 nuclear binding activity. In contrast to the behavior of the mRNA, we noted surprising stability in the levels of total nuclear TR binding capacity and TR isoform distribution in the transition from hypo- to hyperthyroid states. Calculations based on these and previous data from this laboratory (7) show that the average cellular content of TR beta 2 mRNA in pituitary is 0.6 molecules, whereas the content of TR beta 2 mRNA molecules in extrapituitary tissues is less than 0.007 molecule/cell. A high TR beta 2 protein/mRNA ratio in extrapituitary tissues thus could reflect a rapid turnover of TR beta 2 mRNA compared to TR beta 2 protein. This would explain the widespread distribution of TR beta 2 protein and the scarcity of mRNA in extrapituitary tissues.