A group of 60 institutionalized patients with Down syndrome (DS) and age-sex matched mentally retarded (MR) controls were examined for evidence of thyroid disease. Seventeen DS patients (28%) had goiter, exophthalmos, hyperthyroidism or hypothyroidism, and one MR subject had myxedema. Thyroid autoantibodies were present in 51 of the DS group and 23 of the MR patients. Thyroid function tests, including thyroxine (iodine by column), serum thyrotropin, and T3 resin uptake, were not statistically different when both total groups were compared. Australia antigen was detected in 16 DS patients and in none of the controls. Gamma globulin values were significantly higher in DS patients, particularly those with goiter. It was concluded that DS patients frequently have overt thyroid disease as well as demonstrable thyroid autoantibodies.