Among the previously reported putative nuclear thyroid hormone receptor forms having molecular masses of 56-59 kDa and 45-49 kDa, respectively, only the former can be the endogenous receptor. The latter must be a degradation product because it is virtually absent in rat liver nuclear extracts prepared in the presence of 20% glycerol and 5 mM Mg2+, which inhibit degradation. In the absence of glycerol, the receptor form of lower mass was present in large amounts in nuclear extracts. Sucrose could not replace glycerol as a protective agent, even in the presence of Mg2+. Thus, the endogenous nuclear thyroid hormone receptor appears to be labile under the experimental conditions used in preparing nuclear extracts. The molecular mass of the nuclear receptor was determined to be 57 kDa on the basis of SDS-polyacrylamide gel electrophoresis after photoaffinity labeling of nuclear proteins with (3,5-125I)-labeled thyroxine.