The major physiologic effect of thyroid hormone is thought to be initiated by the binding of T3 to the DNA binding thyroid hormone receptor (TR). The aim of this study has been to characterize the organ specific expression of thyroid hormone receptor mRNA, as well as its protein distribution and molecular weight in man. Determination of TRα1, α2, β1 and β2 mRNA molecular size was performed using Northern blot analysis in the human heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. TRα1, α2 and β1 protein expression was characterized by Western blot analysis of human tissues. TRα1 mRNA of 4.9 kb was detected in all 8 tissues analyzed, with varying abundance in the various tissues. TRα2 mRNA was detected in 2 different sizes, with higher intensity at 5.7 and lower intensity at 3.2 kb. There were, however, multiple TRβ1 mRNA of 8, 2 and 1 kb detected. TRβ1 transcripts of 2 kb and 1 kb showed an organ specific pattern of expression. Multiple TRβ2 mRNA of 6.6, 5.2, 2.5 and 2.4 kb were detected, as well as a unique 1 kb transcript, in the heart. TRβ2 transcripts also displayed tissue specific expression. Western blot analysis displayed a single band of 48 kD for TRα1. The abundance of the TRα1 immunoreactive band was highest in the heart, brain, kidney and skeletal muscle, and lowest in the liver, placenta and lung, while no signals were detected in the spleen. The TRα2 specific antibody detected a band of 58 kD in all the tissues analyzed. The relative intensity of the immunoreactive TRα2 band detected was highest in the placenta and lung, with a medium concentration range in skeletal muscle, the heart and kidney. The TRα2 protein concentration was lowest in the spleen, liver and brain. Human TRβ1 protein was detected as 55 and 52 kD bands, as well as a unique band of 45 kD in heart. The 52 kD band was detected in all tissues except the kidney and spleen. The 55 kD band was not detected in the brain or liver. Both the 55 and 52 kD TRβ1 immunoreactive bands were detected in the placenta, lung, heart and skeletal muscle with similar intensity.In conclusion, specific patterns of TR mRNA and protein expression revealed characteristic organ distributions of each subtype. Unique cardiac expression was observed for TRβ₂ mRNA and for TRβ₁ protein.