We recently described the presence of a thyroid-stimulating hormone receptor (TSH-R) variant in orbital tissues. Although the presence of this TSH-R variant could provide the antigenic link between the thyroid and the orbit in Graves' disease and thyroid-associated ophthalmopathy (TAO), the etiopathophysiological significance of this finding remains to be elucidated. Graves' disease and TAO are autoimmune diseases which are likely to be caused by a breakdown of tolerance. We therefore investigated the presence of this variant TSH-R transcript in human thymus. Using primers specific for this variant in reverse polymerase chain reaction (PCR) experiments, Southern blotting, and sequencing of the PCR products we demonstrate the presence of this transcript in RNA extracted from normal human thymus of a 2-year-old child. We were also able to amplify this variant TSH-R transcript from a normal human thyroid cDNA library, but not from an epithelial thymus library. The presence of the variant TSH-R transcript in RNA prepared from normal human thymus suggests that induction of immunological tolerance against this variant TSH-R transcript in the thymus is possible. A lack of tolerance induction for this variant TSH-R transcript could provide an explanation for a possible antigenic link between Graves' disease and TAO.