In this study we have correlated peripheral T cell subset phenotypes with intrathyroidal lymphocyte accumulation in patients with autoimmune thyroid disease (Graves' and Hashimoto's disease). Our study utilized euthyroid family members for one of our control groups (n= 48) thus significantly limiting familial, but not disease-specific, influences on these T cell phenotypes. Our principal new observations were found only in patients with Graves' disease. As previously reported, there was a decrease in CD8 f (suppressor/cytotoxic) T cells in the peripheral blood of patients with untreated hyperthyroid Graves' disease (n = 27) (mean±SEM, 19±1.1% in patients compared with 25±1.2% in controls,p= 0.03). a finding not observed in treated, euthyroid Graves' disease patients or their relatives. However, the relative number of CD8 + T cells, assessed by CD4CD8 ratios, was increased in the intrathyroidal T cell populations (n= lo), when compared to normal and patient peripheral blood. There were no consistent changes in total CD4f (helper) T cells in the peripheral blood of patients with treated and untreated Graves' disease but a reduction in CD4 + 2H4 + (suppressor-inducer) T cells was seen in patients undergoing surgery for Graves' disease (13±6.9% compared with 39±3.4%). Again, however, this T cell subset was increased within the target organ of the same patients (41±5.9%).These data point to either a selective accumulation, or a specific“homing”, of certain T cell subsets within the thyroid gland of patients with Graves' disease where T cell differentiation may be strongly influenced by antithyroid drug treatment and the local immune environment.