Insulin binding to isolated fat cells from rats rendered hyperthyroid by daily injections of T4 (1 mg/kg) for 5 days was approximately doubled. The Scatchard curves reflected a large increase in receptor number, as well as an elevation in affinity of the high affinity binding sites. The response to insulin of the fat cells, however, was not increased accordingly: glucose incorporation into lipid in the presence of insulin did not differ significantly from that observed in the control group, whereas the effect of insulin on the lipolytic response to isoprenaline (isoproterenol) was even reduced in the T4-treated animals. T4 treatment had thus dissociated insulin binding from the metabolic effects of insulin, since the increase in membrane receptors was not paralleled by an enhanced effect of the hormone. Since levels of serum insulin were increased in the treated animals, the increase in number of insulin receptors was not mediated by reduced exposure to insulin. Propranolol failed to fully antagonize the effect of T4 on insulin binding, and reserpine treatment even enhanced it. It seems unlikely, therefore, that the increase in insulin receptors of adipocytes results from an augmented response to endogenous catecholamines in T4-treated rats.