Serum ferritin measurements were evaluated as a marker of thyroid hormone action on peripheral tissues. Mean serum ferritin concentrations were not significantly different in euthyroid, thyrotoxic, and hypothyroid subjects due to a wide spread in ferritin levels among individuals. Intraindividual changes in serum ferritin, however, occurred with changing thyroid function. All 18 patients with thyrotoxic Graves' disease had a decrease in serum ferritin levels when they became euthyroid during antithyroid drug therapy. Furthermore, a significant intraindividual correlation between serum levels of ferritin and T4 or T3 was found in 2 patients with thyrotoxic Graves' disease in whom levels were measured serially throughout the course of therapy. Similarly, serum ferritin levels increased in all 12 hypothyroid patients with Hashimoto's disease when euthyroidism was achieved with L-T4 therapy. Administration of 75 micrograms T3 daily for 1 week to 11 euthyroid subjects resulted in a 23-243% (mean +/- SD, 117 +/- 70%) increase in serum ferritin above basal values. In contrast, in 3 patients with thyroid hormone resistance, the same treatment produced rises in serum ferritin concentrations of only 2%, 5%, and 15%. Our data suggest that alterations in thyroid status in a given individual produce changes in serum ferritin levels. Measurement of this protein before and after T3 therapy may prove useful in the diagnosis of thyroid hormone resistance.