Inheritance of Graves' disease has been linked to the HLA-DR3 gene product which may function in some specific way in antigen presentation. To determine whether the first extracellular domain of this protein, which is specifically involved in antigen presentation, has the same sequence in patients with Graves' disease and in normal individuals, we have amplified the second exon using the polymerase chain reaction, and then cloned and sequenced the DNA segment. In eight subjects with Graves' disease, sequences identical to prototypic reported sequence for DRB 1*0301 were recovered, and in two individuals sequences varied by a few nucleotides, leading to 1-3 amino acid substitutions which did not occur in a pattern. Sequences identical to the prototypic sequence known as DRB3*0101, also previously known as DRw52, were also recovered. Thus the HLA-DRB1 and B3 genes present in patients with autoimmune disease appear to be the same as those present in the general population. These observations indicate that a unique allele is not present in patients with autoimmune disease, but rather that the normal DR3 allele itself, in a manner yet to be described, increases the probability of developing autoimmune thyroid disease.