In the first part of this study, we examined TSH receptor (TSHR) and thyroid hormone receptor (T3R beta) messenger ribonucleic acid (mRNA) levels in normal, hyperplastic, and neoplastic human thyroid tissue. Tumor specimens from patients with different thyroid carcinomas and thyroid adenomas, and tissues from patients with Graves' disease and from normal thyroid glands were analyzed by solution hybridization and Northern blot using complementary RNA probes. In the second part of the study, mRNA analysis of T3R was extended to include the expression levels of each of the four T3R isoforms alpha 1, alpha 2, beta 1, and beta 2. In neoplastic thyroid tissue such as papillary and follicular carcinomas, the expression of both TSHR and T3R beta mRNA per microgram total RNA was significantly lower than that in normal thyroid tissue. The decrease in T3R beta mRNA was shown to represent a specific and significant decrease in T3R beta 2 mRNA levels in particular, but also in the expression levels of T3R beta 1 mRNA. No differences were found in the expression levels of T3R alpha 1 or -alpha 2 mRNA. Furthermore, no differences in TSHR or T3R mRNA levels were found in thyroid tissue from patients with Graves' disease compared to normal thyroid tissue. It is concluded that the reduction of TSHR and T3R mRNA in specific neoplastic thyroid tissues might be associated with the differentiation state of these tumors and that the decrease in T3R mRNA levels is due to a specific decrease in the expression levels of the T3R beta gene.