Human lymphocytes are known to play a critical role in autoimmune diseases both by producing antibodies and by participating in lymphokine-cellular interactions. TSH, a classic pituitary hormone, may be secreted by human lymphocytes, and controversy has existed whether a specific, authentic TSH receptor also was present on the surface of these cells. The objective of our study was to identify TSH receptor transcripts after designing specific oligonucleotides that would recognize a unique putative TSH binding area of the thyroidal TSH receptor. The existence of TSH receptor transcripts was probed by employing these primers in a PCR reaction with cDNA derived from normal peripheral human lymphocytes and human thyroid tissue, as well as with cDNA from a medullary cancer cell line and rat liver. Human lymphocytes and thyroid tissue, but not medullary cancer cells or rat liver, demonstrated specific TSH receptor amplification product both by ethidium bromide staining and by Southern blot hybridization with labeled TSH receptor cDNA. The lymphocyte cDNA was partially sequenced and found to be identical to the thyroid-derived cDNA. These findings indicate that normal, nonactivated, human lymphocytes produce transcript for a TSH receptor that appears identical to that in thyroid tissue. Future studies should focus on the regulation of this transcript, as well as on the role TSH and TSH receptor may play in modulating local lymphokine activation of T and B cells, both in normal conditions and in autoimmune thyroid disease.