In light of new techniques for measuring circulating thyroid hormones and for studying the thyroid gland, we present our experience with 35 patients with solitary autonomous nodules of the thyroid to define more precisely the clinical course of patients with this disorder. The patients ranged in age from 19 to 80 years and 31 of the 35 were female. Younger patients were generally euthyroid and sought attention because of a thyroid mass; virtually all older patients were hyperthyroid. Eighteen had obvious clinical features of hyperthyroidism and 5 over age 70 had apathetic hyperthyroidism; all 5 of the elderly and 13 of the 18 under age 70 had elevated thyroxine (T4) and triiodothyronine (T3) levels. Isolated elevation of T3and elevated basal metabolic rate were observed in 5 previously untreated clinically hyperthyroid young patients. In each of these, thyroid uptake of131I was not suppressible with exogenous T3and BMR was elevated in those tested. Two elderly patients, who had previously been treated for conventional hyperthyroidism with radioactive iodine, had T3toxicosis when hyperthyroidism recurred. There was a strong positive correlation between the age of the patient, the size of the nodule and the thyroid functional state. The mean area of the nodules projected on131I rectilinear scan for euthyroid patients was 5.1 cm2. The mean area of the nodules in hyperthyroid subjects was significantly higher, 13.4 cm2in patients with T3toxicosis and 19.3 cm2in subjects with conventional hyperthyroidism. Progression from a euthyroid state to hyperthyroidism was observed in four patients. One of these became thyrotoxic within days after an injection of iodinated contrast medium. Spontaneous resolution of nodules occurred in two patients.