High affinity TSH binding has been reported in a variety of tissues other than the thyroid, most commonly in adipocytes and lymphocytes. This extrathyroidal binding of TSH has been documented most carefully in the guinea pig epididymal fat pad, where it has been postulated to be due to the presence of the TSH receptor (TSH-R). Extrathyroidal TSH-R expression has also been theorized to account for the associated dermopathy and ophthalmopathy seen in some patients with Graves' disease. We have isolated a cDNA encoding a fragment of the guinea pig TSH-R and have used this as a probe to study the distribution of TSH-R mRNA in the guinea pig. We show here that TSH-R mRNA is expressed in most white adipose tissues and in all brown adipose tissues tested. However, no expression was detectable by Northern analysis or in most polymerase chain reaction experiments using guinea pig retroorbital tissues, bringing into question the proposed role of the TSH-R as an autoantigen in autoimmune ophthalmopathy. The presence of significant amounts of TSH-R mRNA in most adipose tissues suggests a more important role for TSH in lipolysis and thermogenesis than previously thought.