We have studied possible premonitory features of Graves' disease among offspring of parents who had this condition. One-hundred-fifty-three children of parents with Graves' disease were examined, as were 129 control children selected on the basis of a negative history for Graves' disease among first-degree relatives. Examination consisted of a physical examination, brief medical history, and determination of a variety of thyroid function and autoimmunity tests. Thirty-six percent of children of parents with Graves' disease had one or more abnormality, as compared to 24% of the control children. The incidence of abnormalities increased with age and were more common in females. The abnormalities in both groups were similar in variety and intensity, and differed mainly quantitatively in frequency. Half of the minor abnormalities detected in the thyroid, including firmness, enlargement, or lobulations, were accompanied by chemical abnormalities such as a high or low T 4 level, abnormal thyroglobulin or triiodothyronine (T 3) level, or the presence of antithyroid antibodies. One quarter of children having some minor abnormality in the thyroid had definite evidence of Hashimoto's thyroiditis. Bioassays for long-acting thyroid stimulator (LATS) were positive in 2 of 95 children of parents with Graves' disease, and in 1 of 49 control children. Assays for thyroid stimulatory immunoglobulins, cell-mediated immunity to thyroid antigens, and thyroglobulin immune complexes were negative. There was a clustering of abnormalities in certain families, suggesting that these families may be prone to develop subsequent clinical illness. During follow-up examination extending over 3 yr, a significant fraction of children lost or modified the original abnormality or developed a new abnormality. During observation, one child developed asymptomatic thyrotoxicosis, one developed exophthalmos, one developed vitiligo, and one had the onset of Hashimoto's thyroiditis. The data suggest that there is a progressive evolution of abnormalities in thyroid function, and that these are especially common within certain families. It may be possible to determine from sequential examinations which children are at risk, with a high degree of probability of developing thyrotoxicosis. The abnormalities found in these children change from year to year and do not represent a necessarily progressive process. The data indicate the presence of a condition that may be called “Pre-Graves' Disease”, a dynamic state of disordered antithyroid immunity, which may lead to overt thyrotoxicosis in some children.