Biological responses to thyroid hormones are mediated by the nuclear thyroid hormone receptor (TR). Alterations in the maximal triiodothyronine (T3)-binding capacity (Cmax) of TR measured using a ligand binding assay have been reported under some pathophysiological conditions. Northern blot analysis has indicated that TR mRNA concentrations do not necessarily correlate with Cmax levels. For example, although the decrease in Cmax in rat liver induced by prolonged fasting is well established, TR mRNA concentrations have been reported to be constant. In the present study, we examined starvation-induced changes in TR by Western blot with anti-TR(alpha 1 + beta)antiserum and by Scatchard plot analysis. Starvation of rats for 72 hours decreased Cmax in the liver to 72.5% of control levels. The 47- and 55-kd TR proteins detected in hepatic nuclear extract by Western blotting also decreased to 64% and 66% of control values, respectively. The starvation-induced changes in Cmax and TR protein levels paralleled the change in total hepatic nuclear protein concentration. These results suggest that the decrease in T3-binding activity of the TR is due to a reduction of the TR protein itself.