In an investigation of thyroxine (T4) and triiodothyronine (T3) receptors in humans, the lymphocyte was chosen as the target cell. This study was performed to elucidate whether T3 and T4 bind to different receptors, if T4 is bound only after conversion into T3, and whether there is any modification of the receptors in hyper- and hypothyroidism. Lymphocytes were found to possess a high-affinity, limited-capacity bindings sites for both T4 and T3. The mean equilibrium affinity constant (Ka) was 2.28-10(10 +/- 0.21 m-1 for T3, and 0.98 - 10(10) +/- 0.16 m-1 for T4. The mean number of saturable binding sites was 115 for T3, and 102 for T4. The binding capacities and affinities also determined in the lymphocyte nuclei isolated after incubation of the intact cell, were similar to those observed in the intact cells. In competition experiments, labelled T4 was as readily displaced by T3 as by T4 itself, whereas labelled T3 was displaced only by a 40 times higher concentration of T4 than T3. These observations suggest identical receptors for the two hormones and a binding of T4 as such, provided it is not in competition with T3. In lymphocytes from hyperthyroid patients, receptor affinities and numbers remained unchanged. In lymphocytes from hypothyroid patients, the affinity was normal, but the mean number of T3 binding sites was increased to 310 (P less than 0.0001), to return to normal after a few months of treatment.